Filling in the gaps in PARP inhibitor-induced synthetic lethality

Tumors with loss of breast cancer type 1 susceptibility protein (BRCA1) are homologous recombination (HR) deficient and hypersensitive to poly(ADP-ribose) polymerase inhibitors (PARPi). However, these tumors may restore HR and acquire PARPi resistance via loss of end-protection of DNA double-strand...

Full description

Saved in:
Bibliographic Details
Published inMolecular & cellular oncology Vol. 8; no. 6; p. 2010512
Main Authors Paes Dias, Mariana, Jonkers, Jos
Format Journal Article
LanguageEnglish
Published United States Taylor & Francis 2021
Taylor & Francis Group
Subjects
BRCA1/2
drug resistance
PARP inhibitors
ssDNA gaps
BRCA1/2
ssDNA gaps
drug resistance
PARP inhibitors
Online AccessGet full text

Cover

More Information
Summary:Tumors with loss of breast cancer type 1 susceptibility protein (BRCA1) are homologous recombination (HR) deficient and hypersensitive to poly(ADP-ribose) polymerase inhibitors (PARPi). However, these tumors may restore HR and acquire PARPi resistance via loss of end-protection of DNA double-strand breaks. We found that loss of nuclear DNA ligase III resensitizes HR-restored BRCA1-deficient cells to PARPi by exposing post-replicative single-stranded DNA (ssDNA) gaps. Our work, and that of others, identifies ssDNA gaps as a key determinant of PARPi response.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:2372-3556
2372-3556
DOI:10.1080/23723556.2021.2010512