DNA-PKcs Ser2056 auto-phosphorylation is affected by an O-GlcNAcylation/phosphorylation interplay

DNA dependent Protein Kinase (DNA-PK) is an heterotrimeric complex regulating the Non Homologous End Joining (NHEJ) double strand break (DSB) repair pathway. The activity of its catalytic subunit (DNA-PKcs) is regulated by multiple phosphorylations, like the Ser2056 one that impacts DSB end processi...

Full description

Saved in:

Bibliographic Details
Published in	Biochimica et biophysica acta. General subjects Vol. 1864; no. 12; p. 129705
Main Authors	Lafont, Florian, Fleury, Fabrice, Benhelli-Mokrani, Houda
Format	Journal Article
Language	English
Published	Netherlands Elsevier B.V 01.12.2020 Elsevier
Subjects	Acetylglucosamine - metabolism Acylation DNA DNA damage DNA repair DNA-Activated Protein Kinase - metabolism DNA-PKcs genome HeLa Cells human cell lines Humans Life Sciences NHEJ O-GlcNAcylation Phosphorylation post-translational modification protein kinases Protein Processing, Post-Translational protein subunits telomeres DNA-PKcs O-GlcNAcylation Phosphorylation HR NHEJ DNA repair
Online Access	Get full text

Cover

Loading…

Abstract	DNA dependent Protein Kinase (DNA-PK) is an heterotrimeric complex regulating the Non Homologous End Joining (NHEJ) double strand break (DSB) repair pathway. The activity of its catalytic subunit (DNA-PKcs) is regulated by multiple phosphorylations, like the Ser2056 one that impacts DSB end processing and telomeres integrity. O-GlcNAcylation is a post translational modification (PTM) closely related to phosphorylation and its implication in the modulation of DNA-PKcs activity during the DNA Damage Response (DDR) is unknown. Using IP techniques, and HeLa cell line, we evaluated the effect of pharmacological or siOGT mediated O-GlcNAc level modulation on DNA-PKcs O-GlcNAcylation. We used the RPA32 phosphorylation as a DNA-PKcs activity reporter substrate to evaluate the effect of O-GlcNAc modulators. We show here that human DNA-PKcs is an O-GlcNAc modified protein and that this new PTM is responsive to the cell O-GlcNAcylation level modulation. Our findings reveal that DNA-PKcs hypo O-GlcNAcylation affects its kinase activity and that the bleomycin-induced Ser2056 phosphorylation, is modulated by DNA-PKcs O-GlcNAcylation. DNA-PKcs Ser2056 phosphorylation is antagonistically linked to DNA-PKcs O-GlcNAcylation level modulation. Given the essential role of DNA-PKcs Ser2056 phosphorylation in the DDR, this study brings data about the role of cell O-GlcNAc level on genome integrity maintenance. [Display omitted] •Human DNA-PKcs is O-GlcNAc modified.•Lower DNA-PKcs O-GlcNAcylation decreases its kinase activity.•Higher DNA-PKcs O-GlcNAcylation has no effect on its kinase activity.•Pharmacological modulation of DNA-PKcs O-GlcNAcylation affects its Ser2056 Phosphorylation in an antagonistic manner.•DNA-PKcs PSer2056 regulation model: Antagonistic interplay between DNA-PKcs Ser2056 Phosphorylation and the O-GlcNAcylation of a proximal in silico predicted site.
AbstractList	DNA dependent Protein Kinase (DNA-PK) is an heterotrimeric complex regulating the Non Homologous End Joining (NHEJ) double strand break (DSB) repair pathway. The activity of its catalytic subunit (DNA-PKcs) is regulated by multiple phosphorylations, like the Ser2056 one that impacts DSB end processing and telomeres integrity. O-GlcNAcylation is a post translational modification (PTM) closely related to phosphorylation and its implication in the modulation of DNA-PKcs activity during the DNA Damage Response (DDR) is unknown.BACKGROUNDDNA dependent Protein Kinase (DNA-PK) is an heterotrimeric complex regulating the Non Homologous End Joining (NHEJ) double strand break (DSB) repair pathway. The activity of its catalytic subunit (DNA-PKcs) is regulated by multiple phosphorylations, like the Ser2056 one that impacts DSB end processing and telomeres integrity. O-GlcNAcylation is a post translational modification (PTM) closely related to phosphorylation and its implication in the modulation of DNA-PKcs activity during the DNA Damage Response (DDR) is unknown.Using IP techniques, and HeLa cell line, we evaluated the effect of pharmacological or siOGT mediated O-GlcNAc level modulation on DNA-PKcs O-GlcNAcylation. We used the RPA32 phosphorylation as a DNA-PKcs activity reporter substrate to evaluate the effect of O-GlcNAc modulators.METHODSUsing IP techniques, and HeLa cell line, we evaluated the effect of pharmacological or siOGT mediated O-GlcNAc level modulation on DNA-PKcs O-GlcNAcylation. We used the RPA32 phosphorylation as a DNA-PKcs activity reporter substrate to evaluate the effect of O-GlcNAc modulators.We show here that human DNA-PKcs is an O-GlcNAc modified protein and that this new PTM is responsive to the cell O-GlcNAcylation level modulation. Our findings reveal that DNA-PKcs hypo O-GlcNAcylation affects its kinase activity and that the bleomycin-induced Ser2056 phosphorylation, is modulated by DNA-PKcs O-GlcNAcylation.RESULTSWe show here that human DNA-PKcs is an O-GlcNAc modified protein and that this new PTM is responsive to the cell O-GlcNAcylation level modulation. Our findings reveal that DNA-PKcs hypo O-GlcNAcylation affects its kinase activity and that the bleomycin-induced Ser2056 phosphorylation, is modulated by DNA-PKcs O-GlcNAcylation.DNA-PKcs Ser2056 phosphorylation is antagonistically linked to DNA-PKcs O-GlcNAcylation level modulation.CONCLUSIONSDNA-PKcs Ser2056 phosphorylation is antagonistically linked to DNA-PKcs O-GlcNAcylation level modulation.Given the essential role of DNA-PKcs Ser2056 phosphorylation in the DDR, this study brings data about the role of cell O-GlcNAc level on genome integrity maintenance.GENERAL SIGNIFICANCEGiven the essential role of DNA-PKcs Ser2056 phosphorylation in the DDR, this study brings data about the role of cell O-GlcNAc level on genome integrity maintenance. DNA dependent Protein Kinase (DNA-PK) is an heterotrimeric complex regulating the Non Homologous End Joining (NHEJ) double strand break (DSB) repair pathway. The activity of its catalytic subunit (DNA-PKcs) is regulated by multiple phosphorylations, like the Ser2056 one that impacts DSB end processing and telomeres integrity. O-GlcNAcylation is a post translational modification (PTM) closely related to phosphorylation and its implication in the modulation of DNA-PKcs activity during the DNA Damage Response (DDR) is unknown. Using IP techniques, and HeLa cell line, we evaluated the effect of pharmacological or siOGT mediated O-GlcNAc level modulation on DNA-PKcs O-GlcNAcylation. We used the RPA32 phosphorylation as a DNA-PKcs activity reporter substrate to evaluate the effect of O-GlcNAc modulators. We show here that human DNA-PKcs is an O-GlcNAc modified protein and that this new PTM is responsive to the cell O-GlcNAcylation level modulation. Our findings reveal that DNA-PKcs hypo O-GlcNAcylation affects its kinase activity and that the bleomycin-induced Ser2056 phosphorylation, is modulated by DNA-PKcs O-GlcNAcylation. DNA-PKcs Ser2056 phosphorylation is antagonistically linked to DNA-PKcs O-GlcNAcylation level modulation. Given the essential role of DNA-PKcs Ser2056 phosphorylation in the DDR, this study brings data about the role of cell O-GlcNAc level on genome integrity maintenance. DNA dependent Protein Kinase (DNA-PK) is an heterotrimeric complex regulating the Non Homologous End Joining (NHEJ) double strand break (DSB) repair pathway. The activity of its catalytic subunit (DNA-PKcs) is regulated by multiple phosphorylations, like the Ser2056 one that impacts DSB end processing and telomeres integrity. O-GlcNAcylation is a post translational modification (PTM) closely related to phosphorylation and its implication in the modulation of DNA-PKcs activity during the DNA Damage Response (DDR) is unknown.Using IP techniques, and HeLa cell line, we evaluated the effect of pharmacological or siOGT mediated O-GlcNAc level modulation on DNA-PKcs O-GlcNAcylation. We used the RPA32 phosphorylation as a DNA-PKcs activity reporter substrate to evaluate the effect of O-GlcNAc modulators.We show here that human DNA-PKcs is an O-GlcNAc modified protein and that this new PTM is responsive to the cell O-GlcNAcylation level modulation. Our findings reveal that DNA-PKcs hypo O-GlcNAcylation affects its kinase activity and that the bleomycin-induced Ser2056 phosphorylation, is modulated by DNA-PKcs O-GlcNAcylation.DNA-PKcs Ser2056 phosphorylation is antagonistically linked to DNA-PKcs O-GlcNAcylation level modulation.Given the essential role of DNA-PKcs Ser2056 phosphorylation in the DDR, this study brings data about the role of cell O-GlcNAc level on genome integrity maintenance. DNA dependent Protein Kinase (DNA-PK) is an heterotrimeric complex regulating the Non Homologous End Joining (NHEJ) double strand break (DSB) repair pathway. The activity of its catalytic subunit (DNA-PKcs) is regulated by multiple phosphorylations, like the Ser2056 one that impacts DSB end processing and telomeres integrity. O-GlcNAcylation is a post translational modification (PTM) closely related to phosphorylation and its implication in the modulation of DNA-PKcs activity during the DNA Damage Response (DDR) is unknown. Using IP techniques, and HeLa cell line, we evaluated the effect of pharmacological or siOGT mediated O-GlcNAc level modulation on DNA-PKcs O-GlcNAcylation. We used the RPA32 phosphorylation as a DNA-PKcs activity reporter substrate to evaluate the effect of O-GlcNAc modulators. We show here that human DNA-PKcs is an O-GlcNAc modified protein and that this new PTM is responsive to the cell O-GlcNAcylation level modulation. Our findings reveal that DNA-PKcs hypo O-GlcNAcylation affects its kinase activity and that the bleomycin-induced Ser2056 phosphorylation, is modulated by DNA-PKcs O-GlcNAcylation. DNA-PKcs Ser2056 phosphorylation is antagonistically linked to DNA-PKcs O-GlcNAcylation level modulation. Given the essential role of DNA-PKcs Ser2056 phosphorylation in the DDR, this study brings data about the role of cell O-GlcNAc level on genome integrity maintenance. [Display omitted] •Human DNA-PKcs is O-GlcNAc modified.•Lower DNA-PKcs O-GlcNAcylation decreases its kinase activity.•Higher DNA-PKcs O-GlcNAcylation has no effect on its kinase activity.•Pharmacological modulation of DNA-PKcs O-GlcNAcylation affects its Ser2056 Phosphorylation in an antagonistic manner.•DNA-PKcs PSer2056 regulation model: Antagonistic interplay between DNA-PKcs Ser2056 Phosphorylation and the O-GlcNAcylation of a proximal in silico predicted site.
ArticleNumber	129705
Author	Benhelli-Mokrani, Houda Fleury, Fabrice Lafont, Florian
Author_xml	– sequence: 1 givenname: Florian surname: Lafont fullname: Lafont, Florian – sequence: 2 givenname: Fabrice surname: Fleury fullname: Fleury, Fabrice – sequence: 3 givenname: Houda surname: Benhelli-Mokrani fullname: Benhelli-Mokrani, Houda email: Houda.benhelli@univ-nantes.fr
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/32805318$$D View this record in MEDLINE/PubMed https://hal.science/hal-03492304$$DView record in HAL
BookMark	eNqNkV9rFDEUxYNU7Lb6DUTmUR9mm_8z44OwVNuKSyuoz-Emc8dmmZ1sk9nCfnuznW0fFNQL4cLldw7hnBNyNIQBCXnN6JxRps9Wc2vhJw5zTnk-8aai6hmZsbriZU2pPiIzKqgsJdPqmJyktKJ5VKNekGPBa6oEq2cEPl4vyq9fXCq-YeRU6QK2Yyg3tyHlF3c9jD4MhU8FdB26EdvC7goYipvysnfXC3cgzv5QDCPGTQ-7l-R5B33CV4d9Sn5cfPp-flUuby4_ny-WpZOVGktkSiK1jiFqW2mlLBOt4BwqZ0E3NW1QtFZLplqEVkIGG847VomaW9RanJJ3k-8t9GYT_RrizgTw5mqxNPsbFbLhOZF7ltm3E7uJ4W6LaTRrnxz2PQwYtslwpVjDJa_-A5XigVV1Rt8c0K1dY_v0ice0M_B-AlwMKUXsjPPjQ1xjBN8bRs2-WrMyU7VmX62Zqs1i-Zv40f8fsg-TDHP29x6jSc7j4LD1Mfdp2uD_bvALl4m85A
CitedBy_id	crossref_primary_10_1021_acs_chemrev_4c00417 crossref_primary_10_1016_j_canlet_2024_217101 crossref_primary_10_1016_j_jbc_2024_107141 crossref_primary_10_3390_genes12071091 crossref_primary_10_1002_mco2_613 crossref_primary_10_31857_S0320972524060113 crossref_primary_10_1016_j_bbamcr_2024_119828 crossref_primary_10_1134_S0006297924060117 crossref_primary_10_1016_j_ijbiomac_2024_130351
Cites_doi	10.1016/j.bbagen.2012.06.013 10.1016/S0021-9258(17)43295-9 10.1038/nature05815 10.1007/s000180300017 10.1016/j.dnarep.2010.09.019 10.1093/emboj/18.5.1397 10.1158/1541-7786.MCR-18-1025 10.1016/j.bbrc.2019.10.133 10.1021/bi0263558 10.1038/sj.emboj.7601255 10.1016/j.cell.2014.01.061 10.1073/pnas.1009023107 10.1016/S0304-4165(02)00477-4 10.1128/MCB.01554-13 10.1002/pmic.201400339 10.1016/j.sbi.2008.09.005 10.1007/s00726-010-0695-z 10.1093/nar/gkh508 10.1093/nar/27.17.3494 10.1016/j.mrfmmm.2011.02.010 10.1128/MCB.02366-06 10.1097/ACI.0b013e3283327e41 10.1158/0008-5472.CAN-08-2854 10.1128/MCB.01298-10 10.1146/annurev-biochem-060608-102511 10.1016/0092-8674(93)90057-W 10.1083/jcb.201501101 10.1038/ncb1470 10.1016/j.celrep.2020.107632
ContentType	Journal Article
Copyright	2020 Copyright © 2020. Published by Elsevier B.V. Attribution - NonCommercial
Copyright_xml	– notice: 2020 – notice: Copyright © 2020. Published by Elsevier B.V. – notice: Attribution - NonCommercial
DBID	AAYXX CITATION CGR CUY CVF ECM EIF NPM 7X8 7S9 L.6 1XC VOOES
DOI	10.1016/j.bbagen.2020.129705
DatabaseName	CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic AGRICOLA AGRICOLA - Academic Hyper Article en Ligne (HAL) Hyper Article en Ligne (HAL) (Open Access)
DatabaseTitle	CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic AGRICOLA AGRICOLA - Academic
DatabaseTitleList	MEDLINE - Academic MEDLINE AGRICOLA
Database_xml	– sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database
DeliveryMethod	fulltext_linktorsrc
Discipline	Chemistry Biology
EISSN	1872-8006
ExternalDocumentID	oai_HAL_hal_03492304v1 32805318 10_1016_j_bbagen_2020_129705 S0304416520302178
Genre	Research Support, Non-U.S. Gov't Journal Article
GroupedDBID	--- --K --M .~1 0R~ 1B1 1RT 1~. 1~5 23N 3O- 4.4 457 4G. 53G 5GY 5RE 5VS 7-5 71M 8P~ 9JM AACTN AAEDT AAEDW AAIAV AAIKJ AAKOC AALRI AAOAW AAQFI AAQXK AAXUO ABEFU ABFNM ABGSF ABMAC ABUDA ABXDB ABYKQ ACDAQ ACIUM ACRLP ADBBV ADEZE ADMUD ADUVX AEBSH AEHWI AEKER AFKWA AFTJW AFXIZ AGHFR AGRDE AGUBO AGYEJ AHHHB AIEXJ AIKHN AITUG AJBFU AJOXV ALMA_UNASSIGNED_HOLDINGS AMFUW AMRAJ ASPBG AVWKF AXJTR AZFZN BKOJK BLXMC CS3 DOVZS EBS EFJIC EFLBG EJD EO8 EO9 EP2 EP3 FDB FEDTE FGOYB FIRID FNPLU FYGXN G-2 G-Q GBLVA HLW HVGLF HZ~ IHE J1W KOM LX3 M41 MO0 N9A O-L O9- OAUVE OHT OZT P-8 P-9 PC. Q38 R2- ROL RPZ SBG SCC SDF SDG SDP SES SEW SPCBC SSU SSZ T5K UQL WH7 WUQ XJT XPP ~G- AAHBH AATTM AAXKI AAYWO AAYXX ABWVN ACRPL ACVFH ADCNI ADNMO AEIPS AEUPX AFJKZ AFPUW AGCQF AGQPQ AGRNS AIGII AIIUN AKBMS AKRWK AKYEP ANKPU APXCP BNPGV CITATION SSH CGR CUY CVF ECM EIF NPM 7X8 7S9 L.6 1XC VOOES
ID	FETCH-LOGICAL-c475t-e154e0bc1ee6b7655b13d322a7cba69809e3db6415dead4ac1e922f17382be663
IEDL.DBID	.~1
ISSN	0304-4165 1872-8006
IngestDate	Fri May 09 12:14:53 EDT 2025 Fri Jul 11 06:22:58 EDT 2025 Fri Jul 11 15:55:12 EDT 2025 Wed Feb 19 02:30:29 EST 2025 Tue Jul 01 00:22:14 EDT 2025 Thu Apr 24 23:03:33 EDT 2025 Fri Feb 23 02:47:57 EST 2024
IsDoiOpenAccess	true
IsOpenAccess	true
IsPeerReviewed	true
IsScholarly	true
Issue	12
Keywords	DNA-PKcs O-GlcNAcylation Phosphorylation HR NHEJ DNA repair
Language	English
License	Copyright © 2020. Published by Elsevier B.V. Attribution - NonCommercial: http://creativecommons.org/licenses/by-nc
LinkModel	DirectLink
MergedId	FETCHMERGED-LOGICAL-c475t-e154e0bc1ee6b7655b13d322a7cba69809e3db6415dead4ac1e922f17382be663
Notes	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
OpenAccessLink	https://hal.science/hal-03492304
PMID	32805318
PQID	2435192458
PQPubID	23479
ParticipantIDs	hal_primary_oai_HAL_hal_03492304v1 proquest_miscellaneous_2551924271 proquest_miscellaneous_2435192458 pubmed_primary_32805318 crossref_citationtrail_10_1016_j_bbagen_2020_129705 crossref_primary_10_1016_j_bbagen_2020_129705 elsevier_sciencedirect_doi_10_1016_j_bbagen_2020_129705
ProviderPackageCode	CITATION AAYXX
PublicationCentury	2000
PublicationDate	2020-12-01
PublicationDateYYYYMMDD	2020-12-01
PublicationDate_xml	– month: 12 year: 2020 text: 2020-12-01 day: 01
PublicationDecade	2020
PublicationPlace	Netherlands
PublicationPlace_xml	– name: Netherlands
PublicationTitle	Biochimica et biophysica acta. General subjects
PublicationTitleAlternate	Biochim Biophys Acta Gen Subj
PublicationYear	2020
Publisher	Elsevier B.V Elsevier
Publisher_xml	– name: Elsevier B.V – name: Elsevier
References	Hurtado-Guerrero, Dorfmueller, van Aalten (bb0065) 2008; 18 Zhong (bb0115) 2015; 15 Zachara, Molina, Wong, Pandey, Hart (bb0060) 2011; 40 Yang (bb0110) 2006; 8 Neal (bb0020) 2014; 34 Goodarzi (bb0030) 2006; 25 Carmen-Rosa, Hart (bb0070) 1984; 259 Chen, Yu (bb0125) 2016; 44 Hart, Housley, Slawson (bb0100) 2007; 446 Block, Merkle, Meek, Lees-Miller (bb0135) 2004; 32 Bond, Hanover (bb0085) 2015; 208 Gottlieb, Jackson (bb0010) 1993; 72 Meek, Douglas, Cui, Ding, Lees-Miller (bb0025) 2007; 27 Hart, Slawson, Ramirez-Correa, Lagerlof (bb0105) 2011; 80 Dobbs, Tainer, Lees-Miller (bb0035) 2010; 9 Konopka (bb0075) 2012; 2012 Denzel (bb0090) 2014; 156 Neal, Meek (bb0050) 2011; 711 Miura, Sakurai, Endo (bb0120) 2012; 1820 Efimova (bb0145) 2019; 17 Wells, Vosseller, Hart (bb0155) 2003; 60 Sakabe, Wang, Hart (bb0080) 2010; 107 Lefebvre (bb0095) 2003; 1619 Gell, Jackson (bb0005) 1999; 27 Na, Akan, Abramowitz, Hanover (bb0150) 2020; 31 Shao (bb0130) 1999; 18 Van Der Burg, Van Dongen, Van Gent (bb0015) 2009; 9 Neal (bb0045) 2011; 31 Williams (bb0055) 2009; 69 Merkle (bb0040) 2002; 41 Shiga (bb0140) 2019; 521 Merkle (10.1016/j.bbagen.2020.129705_bb0040) 2002; 41 Gottlieb (10.1016/j.bbagen.2020.129705_bb0010) 1993; 72 Bond (10.1016/j.bbagen.2020.129705_bb0085) 2015; 208 Wells (10.1016/j.bbagen.2020.129705_bb0155) 2003; 60 Zachara (10.1016/j.bbagen.2020.129705_bb0060) 2011; 40 Miura (10.1016/j.bbagen.2020.129705_bb0120) 2012; 1820 Denzel (10.1016/j.bbagen.2020.129705_bb0090) 2014; 156 Block (10.1016/j.bbagen.2020.129705_bb0135) 2004; 32 Yang (10.1016/j.bbagen.2020.129705_bb0110) 2006; 8 Neal (10.1016/j.bbagen.2020.129705_bb0020) 2014; 34 Dobbs (10.1016/j.bbagen.2020.129705_bb0035) 2010; 9 Konopka (10.1016/j.bbagen.2020.129705_bb0075) 2012; 2012 Neal (10.1016/j.bbagen.2020.129705_bb0045) 2011; 31 Gell (10.1016/j.bbagen.2020.129705_bb0005) 1999; 27 Meek (10.1016/j.bbagen.2020.129705_bb0025) 2007; 27 Efimova (10.1016/j.bbagen.2020.129705_bb0145) 2019; 17 Shiga (10.1016/j.bbagen.2020.129705_bb0140) 2019; 521 Williams (10.1016/j.bbagen.2020.129705_bb0055) 2009; 69 Hart (10.1016/j.bbagen.2020.129705_bb0100) 2007; 446 Shao (10.1016/j.bbagen.2020.129705_bb0130) 1999; 18 Van Der Burg (10.1016/j.bbagen.2020.129705_bb0015) 2009; 9 Goodarzi (10.1016/j.bbagen.2020.129705_bb0030) 2006; 25 Carmen-Rosa (10.1016/j.bbagen.2020.129705_bb0070) 1984; 259 Hart (10.1016/j.bbagen.2020.129705_bb0105) 2011; 80 Neal (10.1016/j.bbagen.2020.129705_bb0050) 2011; 711 Na (10.1016/j.bbagen.2020.129705_bb0150) 2020; 31 Zhong (10.1016/j.bbagen.2020.129705_bb0115) 2015; 15 Sakabe (10.1016/j.bbagen.2020.129705_bb0080) 2010; 107 Hurtado-Guerrero (10.1016/j.bbagen.2020.129705_bb0065) 2008; 18 Lefebvre (10.1016/j.bbagen.2020.129705_bb0095) 2003; 1619 Chen (10.1016/j.bbagen.2020.129705_bb0125) 2016; 44
References_xml	– volume: 32 start-page: 1967 year: 2004 end-page: 1972 ident: bb0135 article-title: Selective inhibition of the DNA-dependent protein kinase (DNA-PK) by the radiosensitizing agent caffeine publication-title: Nucleic Acids Res. – volume: 9 start-page: 1307 year: 2010 end-page: 1314 ident: bb0035 article-title: A structural model for regulation of NHEJ by DNA-PKcs autophosphorylation publication-title: DNA Repair (Amst) – volume: 107 start-page: 19915 year: 2010 end-page: 19920 ident: bb0080 article-title: -N-acetylglucosamine (O-GlcNAc) is part of the histone code publication-title: Proc. Natl. Acad. Sci. – volume: 60 start-page: 222 year: 2003 end-page: 228 ident: bb0155 article-title: A role for N-acetylglucosamine as a nutrient sensor and mediator of insulin resistance publication-title: Cell. Mol. Life Sci. – volume: 1820 start-page: 1678 year: 2012 end-page: 1685 ident: bb0120 article-title: O-GlcNAc modification affects the ATM-mediated DNA damage response publication-title: Biochim. Biophys. Acta, Gen. Subj. – volume: 1619 start-page: 167 year: 2003 end-page: 176 ident: bb0095 article-title: Evidence of a balance between phosphorylation and O-GlcNAc glycosylation of Tau proteins - a role in nuclear localization publication-title: Biochim. Biophys. Acta, Gen. Subj. – volume: 18 start-page: 1397 year: 1999 end-page: 1406 ident: bb0130 article-title: Replication-mediated DNA damage by camptothecin induces phosphorylation of RPA by DNA-dependent protein kinase and dissociates RPA:DNA-PK complexes publication-title: EMBO J. – volume: 18 start-page: 551 year: 2008 end-page: 557 ident: bb0065 article-title: Molecular mechanisms of O-GlcNAcylation publication-title: Curr. Opin. Struct. Biol. – volume: 34 start-page: 2162 year: 2014 end-page: 2175 ident: bb0020 article-title: Unraveling the complexities of DNA-PK autophosphorylation publication-title: Mol. Cell. Biol. – volume: 711 start-page: 73 year: 2011 end-page: 86 ident: bb0050 article-title: Choosing the right path: does DNA-PK help make the decision? publication-title: Mutat. Res. Fundam. Mol. Mech. Mutagen. – volume: 521 start-page: 668 year: 2019 end-page: 673 ident: bb0140 article-title: DNA-PKcs is activated under nutrient starvation and activates Akt, MST1, FoxO3a, and NDR1 publication-title: Biochem. Biophys. Res. Commun. – volume: 259 start-page: 3308 year: 1984 end-page: 3317 ident: bb0070 article-title: Topography and polypeptide distribution of terminal N-Acetylglucosamine residues on the surfaces of intact lymphocytes publication-title: J. Biol. Chem. – volume: 31 start-page: 1719 year: 2011 end-page: 1733 ident: bb0045 article-title: Inhibition of homologous recombination by DNA-dependent protein kinase requires kinase activity, is titratable, and is modulated by autophosphorylation publication-title: Mol. Cell. Biol. – volume: 156 start-page: 1167 year: 2014 end-page: 1178 ident: bb0090 article-title: Hexosamine pathway metabolites enhance protein quality control and prolong life publication-title: Cell – volume: 446 start-page: 1017 year: 2007 end-page: 1022 ident: bb0100 article-title: Cycling of O-linked β-N-acetylglucosamine on nucleocytoplasmic proteins publication-title: Nature – volume: 44 start-page: 9266 year: 2016 end-page: 9278 ident: bb0125 article-title: OGT restrains the expansion of DNA damage signaling publication-title: Nucleic Acids Res. – volume: 31 year: 2020 ident: bb0150 article-title: Nutrient-driven O-GlcNAcylation controls DNA damage repair signaling and stem/progenitor cell homeostasis publication-title: Cell Rep. – volume: 15 start-page: 591 year: 2015 end-page: 607 ident: bb0115 article-title: Quantitative phosphoproteomics reveals crosstalk between phosphorylation and O-GlcNAc in the DNA damage response pathway publication-title: Proteomics – volume: 27 start-page: 3494 year: 1999 end-page: 3502 ident: bb0005 article-title: Mapping of protein-protein interactions within the DNA-dependent protein kinase complex publication-title: Nucleic Acids Res. – volume: 72 start-page: 131 year: 1993 end-page: 142 ident: bb0010 article-title: The DNA-dependent protein kinase: requirement for DNA ends and association with Ku antigen publication-title: Cell – volume: 208 start-page: 869 year: 2015 end-page: 880 ident: bb0085 article-title: A little sugar goes a long way: the cell biology of O-GlcNAc publication-title: J. Cell Biol. – volume: 17 start-page: 1338 year: 2019 end-page: 1350 ident: bb0145 article-title: O-GlcNAcylation enhances double strand break repair, promotes cancer cell proliferation and prevents therapy-induced senescence in irradiated tumors publication-title: Mol. Cancer Res. – volume: 2012 start-page: 489208 year: 2012 end-page: 489223 ident: bb0075 article-title: N-Acetylglucosamine functions in cell signaling publication-title: Scientifica (Cairo) – volume: 9 start-page: 503 year: 2009 end-page: 509 ident: bb0015 article-title: DNA-PKcs deficiency in human: long predicted, finally found publication-title: Curr. Opin. Allergy Clin. Immunol. – volume: 80 start-page: 825 year: 2011 end-page: 858 ident: bb0105 article-title: Cross talk between O-GlcNAcylation and phosphorylation: roles in signaling, transcription, and chronic disease publication-title: Annu. Rev. Biochem. – volume: 27 start-page: 3881 year: 2007 end-page: 3890 ident: bb0025 article-title: Trans autophosphorylation at DNA-dependent protein kinase’s two major autophosphorylation site clusters facilitates end processing but not end joining publication-title: Mol. Cell. Biol. – volume: 40 start-page: 793 year: 2011 end-page: 808 ident: bb0060 article-title: The dynamic stress-induced ‘o-GlcNAc-ome’ highlights functions for O-GlcNAc in regulating DNA damage/repair and other cellular pathways publication-title: Amino Acids – volume: 41 start-page: 12706 year: 2002 end-page: 12714 ident: bb0040 article-title: The DNA-dependent protein kinase interacts with DNA to form a protein - DNA complex that is disrupted by phosphorylation publication-title: Biochemistry – volume: 8 start-page: 1074 year: 2006 end-page: 1083 ident: bb0110 article-title: Modification of p53 with O-linked N-acetylglucosamine regulates p53 activity and stability publication-title: Nat. Cell Biol. – volume: 25 start-page: 3880 year: 2006 end-page: 3889 ident: bb0030 article-title: DNA-PK autophosphorylation facilitates Artemis endonuclease activity publication-title: EMBO J. – volume: 69 start-page: 2100 year: 2009 end-page: 2107 ident: bb0055 article-title: Telomere dysfunction and DNA-PKcs deficiency: characterization and consequence publication-title: Cancer Res. – volume: 1820 start-page: 1678 year: 2012 ident: 10.1016/j.bbagen.2020.129705_bb0120 article-title: O-GlcNAc modification affects the ATM-mediated DNA damage response publication-title: Biochim. Biophys. Acta, Gen. Subj. doi: 10.1016/j.bbagen.2012.06.013 – volume: 259 start-page: 3308 year: 1984 ident: 10.1016/j.bbagen.2020.129705_bb0070 article-title: Topography and polypeptide distribution of terminal N-Acetylglucosamine residues on the surfaces of intact lymphocytes publication-title: J. Biol. Chem. doi: 10.1016/S0021-9258(17)43295-9 – volume: 446 start-page: 1017 issue: 7139 year: 2007 ident: 10.1016/j.bbagen.2020.129705_bb0100 article-title: Cycling of O-linked β-N-acetylglucosamine on nucleocytoplasmic proteins publication-title: Nature doi: 10.1038/nature05815 – volume: 60 start-page: 222 year: 2003 ident: 10.1016/j.bbagen.2020.129705_bb0155 article-title: A role for N-acetylglucosamine as a nutrient sensor and mediator of insulin resistance publication-title: Cell. Mol. Life Sci. doi: 10.1007/s000180300017 – volume: 9 start-page: 1307 year: 2010 ident: 10.1016/j.bbagen.2020.129705_bb0035 article-title: A structural model for regulation of NHEJ by DNA-PKcs autophosphorylation publication-title: DNA Repair (Amst) doi: 10.1016/j.dnarep.2010.09.019 – volume: 18 start-page: 1397 year: 1999 ident: 10.1016/j.bbagen.2020.129705_bb0130 article-title: Replication-mediated DNA damage by camptothecin induces phosphorylation of RPA by DNA-dependent protein kinase and dissociates RPA:DNA-PK complexes publication-title: EMBO J. doi: 10.1093/emboj/18.5.1397 – volume: 17 start-page: 1338 year: 2019 ident: 10.1016/j.bbagen.2020.129705_bb0145 article-title: O-GlcNAcylation enhances double strand break repair, promotes cancer cell proliferation and prevents therapy-induced senescence in irradiated tumors publication-title: Mol. Cancer Res. doi: 10.1158/1541-7786.MCR-18-1025 – volume: 521 start-page: 668 year: 2019 ident: 10.1016/j.bbagen.2020.129705_bb0140 article-title: DNA-PKcs is activated under nutrient starvation and activates Akt, MST1, FoxO3a, and NDR1 publication-title: Biochem. Biophys. Res. Commun. doi: 10.1016/j.bbrc.2019.10.133 – volume: 41 start-page: 12706 year: 2002 ident: 10.1016/j.bbagen.2020.129705_bb0040 article-title: The DNA-dependent protein kinase interacts with DNA to form a protein - DNA complex that is disrupted by phosphorylation publication-title: Biochemistry doi: 10.1021/bi0263558 – volume: 25 start-page: 3880 year: 2006 ident: 10.1016/j.bbagen.2020.129705_bb0030 article-title: DNA-PK autophosphorylation facilitates Artemis endonuclease activity publication-title: EMBO J. doi: 10.1038/sj.emboj.7601255 – volume: 156 start-page: 1167 year: 2014 ident: 10.1016/j.bbagen.2020.129705_bb0090 article-title: Hexosamine pathway metabolites enhance protein quality control and prolong life publication-title: Cell doi: 10.1016/j.cell.2014.01.061 – volume: 107 start-page: 19915 year: 2010 ident: 10.1016/j.bbagen.2020.129705_bb0080 article-title: -N-acetylglucosamine (O-GlcNAc) is part of the histone code publication-title: Proc. Natl. Acad. Sci. doi: 10.1073/pnas.1009023107 – volume: 1619 start-page: 167 year: 2003 ident: 10.1016/j.bbagen.2020.129705_bb0095 article-title: Evidence of a balance between phosphorylation and O-GlcNAc glycosylation of Tau proteins - a role in nuclear localization publication-title: Biochim. Biophys. Acta, Gen. Subj. doi: 10.1016/S0304-4165(02)00477-4 – volume: 34 start-page: 2162 year: 2014 ident: 10.1016/j.bbagen.2020.129705_bb0020 article-title: Unraveling the complexities of DNA-PK autophosphorylation publication-title: Mol. Cell. Biol. doi: 10.1128/MCB.01554-13 – volume: 15 start-page: 591 year: 2015 ident: 10.1016/j.bbagen.2020.129705_bb0115 article-title: Quantitative phosphoproteomics reveals crosstalk between phosphorylation and O-GlcNAc in the DNA damage response pathway publication-title: Proteomics doi: 10.1002/pmic.201400339 – volume: 18 start-page: 551 year: 2008 ident: 10.1016/j.bbagen.2020.129705_bb0065 article-title: Molecular mechanisms of O-GlcNAcylation publication-title: Curr. Opin. Struct. Biol. doi: 10.1016/j.sbi.2008.09.005 – volume: 40 start-page: 793 year: 2011 ident: 10.1016/j.bbagen.2020.129705_bb0060 article-title: The dynamic stress-induced ‘o-GlcNAc-ome’ highlights functions for O-GlcNAc in regulating DNA damage/repair and other cellular pathways publication-title: Amino Acids doi: 10.1007/s00726-010-0695-z – volume: 32 start-page: 1967 year: 2004 ident: 10.1016/j.bbagen.2020.129705_bb0135 article-title: Selective inhibition of the DNA-dependent protein kinase (DNA-PK) by the radiosensitizing agent caffeine publication-title: Nucleic Acids Res. doi: 10.1093/nar/gkh508 – volume: 27 start-page: 3494 year: 1999 ident: 10.1016/j.bbagen.2020.129705_bb0005 article-title: Mapping of protein-protein interactions within the DNA-dependent protein kinase complex publication-title: Nucleic Acids Res. doi: 10.1093/nar/27.17.3494 – volume: 711 start-page: 73 year: 2011 ident: 10.1016/j.bbagen.2020.129705_bb0050 article-title: Choosing the right path: does DNA-PK help make the decision? publication-title: Mutat. Res. Fundam. Mol. Mech. Mutagen. doi: 10.1016/j.mrfmmm.2011.02.010 – volume: 27 start-page: 3881 year: 2007 ident: 10.1016/j.bbagen.2020.129705_bb0025 article-title: Trans autophosphorylation at DNA-dependent protein kinase’s two major autophosphorylation site clusters facilitates end processing but not end joining publication-title: Mol. Cell. Biol. doi: 10.1128/MCB.02366-06 – volume: 9 start-page: 503 year: 2009 ident: 10.1016/j.bbagen.2020.129705_bb0015 article-title: DNA-PKcs deficiency in human: long predicted, finally found publication-title: Curr. Opin. Allergy Clin. Immunol. doi: 10.1097/ACI.0b013e3283327e41 – volume: 2012 start-page: 489208 year: 2012 ident: 10.1016/j.bbagen.2020.129705_bb0075 article-title: N-Acetylglucosamine functions in cell signaling publication-title: Scientifica (Cairo) – volume: 69 start-page: 2100 year: 2009 ident: 10.1016/j.bbagen.2020.129705_bb0055 article-title: Telomere dysfunction and DNA-PKcs deficiency: characterization and consequence publication-title: Cancer Res. doi: 10.1158/0008-5472.CAN-08-2854 – volume: 31 start-page: 1719 year: 2011 ident: 10.1016/j.bbagen.2020.129705_bb0045 article-title: Inhibition of homologous recombination by DNA-dependent protein kinase requires kinase activity, is titratable, and is modulated by autophosphorylation publication-title: Mol. Cell. Biol. doi: 10.1128/MCB.01298-10 – volume: 44 start-page: 9266 year: 2016 ident: 10.1016/j.bbagen.2020.129705_bb0125 article-title: OGT restrains the expansion of DNA damage signaling publication-title: Nucleic Acids Res. – volume: 80 start-page: 825 year: 2011 ident: 10.1016/j.bbagen.2020.129705_bb0105 article-title: Cross talk between O-GlcNAcylation and phosphorylation: roles in signaling, transcription, and chronic disease publication-title: Annu. Rev. Biochem. doi: 10.1146/annurev-biochem-060608-102511 – volume: 72 start-page: 131 year: 1993 ident: 10.1016/j.bbagen.2020.129705_bb0010 article-title: The DNA-dependent protein kinase: requirement for DNA ends and association with Ku antigen publication-title: Cell doi: 10.1016/0092-8674(93)90057-W – volume: 208 start-page: 869 year: 2015 ident: 10.1016/j.bbagen.2020.129705_bb0085 article-title: A little sugar goes a long way: the cell biology of O-GlcNAc publication-title: J. Cell Biol. doi: 10.1083/jcb.201501101 – volume: 8 start-page: 1074 year: 2006 ident: 10.1016/j.bbagen.2020.129705_bb0110 article-title: Modification of p53 with O-linked N-acetylglucosamine regulates p53 activity and stability publication-title: Nat. Cell Biol. doi: 10.1038/ncb1470 – volume: 31 year: 2020 ident: 10.1016/j.bbagen.2020.129705_bb0150 article-title: Nutrient-driven O-GlcNAcylation controls DNA damage repair signaling and stem/progenitor cell homeostasis publication-title: Cell Rep. doi: 10.1016/j.celrep.2020.107632
SSID	ssj0000595
Score	2.3872147
Snippet	DNA dependent Protein Kinase (DNA-PK) is an heterotrimeric complex regulating the Non Homologous End Joining (NHEJ) double strand break (DSB) repair pathway....
SourceID	hal proquest pubmed crossref elsevier
SourceType	Open Access Repository Aggregation Database Index Database Enrichment Source Publisher
StartPage	129705
SubjectTerms	Acetylglucosamine - metabolism Acylation DNA DNA damage DNA repair DNA-Activated Protein Kinase - metabolism DNA-PKcs genome HeLa Cells human cell lines Humans Life Sciences NHEJ O-GlcNAcylation Phosphorylation post-translational modification protein kinases Protein Processing, Post-Translational protein subunits telomeres
Title	DNA-PKcs Ser2056 auto-phosphorylation is affected by an O-GlcNAcylation/phosphorylation interplay
URI	https://dx.doi.org/10.1016/j.bbagen.2020.129705 https://www.ncbi.nlm.nih.gov/pubmed/32805318 https://www.proquest.com/docview/2435192458 https://www.proquest.com/docview/2551924271 https://hal.science/hal-03492304
Volume	1864
hasFullText	1
inHoldings	1
isFullTextHit
isPrint
link	http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Rb9MwED6NIcRe0BgwCmMyiFfTxnbi5DEqG4VBQYJJe7Nsx9WKqrRa20l94bdzFydFaMAkHiIl1tlOfOfzp_jzHcBraQdOSZ_w3BaBK-0Fd4lT3NukQgORvgp0OPnTOBudqw8X6cUODLuzMESrbH1_9OmNt25L-u1o9hfTaf8rbeohnEgF3iCwpgO_Smmy8jc_ftE8ED6kcSdBcZLujs81HC_ncNJSFFRBYRYKTUns_rw83bkknuTfQGizGJ3uw4MWRbIyvuhD2An1AdyLeSU3B3B_2KVxewT27bjkX878kqFbEAhEmF2v5nxxOV_idbWJXDg2XTLbUDtCxdyG2Zp95u9mflz6VqJ_o0ZDV5zZzWM4Pz35NhzxNq8C90qnKx4QNoWB80kImdNZmrpEVjixrfbOZkU-KIKsXIZLe4V2piwKFkJMEi1z4QJClCewW8_r8BTYBFtKbOGsQ5VPlLDKVZVXEkGEmBS57YHshtP4Nug45b6YmY5d9t1EJRhSgolK6AHf1lrEoBu3yOtOU-Y34zG4LtxS8xUqdtsJxdoelR8NlVHgHvpjfp304GWnd4PKox0VW4f5emmEovyGQqX5P2TSRkRobOcwGs22PylycoL5s__-gOewR0-RYHMEu6urdXiBMGnljpt5cAx3y_dno_FPjnkPkQ
linkProvider	Elsevier
linkToHtml	http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3db9MwED9tndB4QTC-CgwM4tVq4zhfj1HZyGgXkNikvVm242pFVVqtLVL_e-7ipAgxNomHSJFzZye-891P8fkO4GOoh0aGNuCpzhyXiRXcBEZyq4MKFSS0laPDyedlXFzKL1fR1R6MurMwFFbZ2n5v0xtr3bYM2tkcLGezwXfa1EM4EQm8QWCd7sMBZaeKenCQn42L8rdBjpriK0TPiaE7QdeEeRmD65YSoQrKtJAlVMfudg-1f02hkv_CoY0_On0Mj1ogyXL_rk9gz9VH8MCXltweweGoq-T2FPSnMuffxnbF0DIIxCJMb9YLvrxerPC62fpwODZbMd1Ed7iKmS3TNfvKP89tmduWYvAXRxOxONfbZ3B5enIxKnhbWoFbnKE1d4ic3NDYwLnYJHEUmSCscG3rxBodZ-kwc2FlYvTuFaqa1EiYCTENkjAVxiFKeQ69elG7l8Cm2FOgM6MNSn0qhZamqqwMEUeIaZbqPoTddCrb5h2n8hdz1QWY_VBeCIqEoLwQ-sB3XEufd-Me-qSTlPpDfxS6hns4P6Bgd4NQuu0inyhqo9w99NP8Z9CH953cFQqPNlV07RablRKSShwKGaV30EQNiUiwnxdeaXbjhSIlO5i--u8PeAeHxcX5RE3OyvFreEhPfLzNG-itbzbuGFHT2rxtV8Uv1vESQg
openUrl	ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=DNA-PKcs+Ser2056+auto-phosphorylation+is+affected+by+an+O-GlcNAcylation%2Fphosphorylation+interplay&rft.jtitle=Biochimica+et+biophysica+acta.+General+subjects&rft.au=Lafont%2C+Florian&rft.au=Fleury%2C+Fabrice&rft.au=Benhelli-Mokrani%2C+Houda&rft.date=2020-12-01&rft.issn=1872-8006&rft.eissn=1872-8006&rft.volume=1864&rft.issue=12&rft.spage=129705&rft_id=info:doi/10.1016%2Fj.bbagen.2020.129705&rft.externalDBID=NO_FULL_TEXT
thumbnail_l	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0304-4165&client=summon
thumbnail_m	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0304-4165&client=summon
thumbnail_s	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0304-4165&client=summon