RecQ4 Facilitates UV Light-induced DNA Damage Repair through Interaction with Nucleotide Excision Repair Factor Xeroderma Pigmentosum Group A (XPA)

Mutations in the RECQL4 helicase gene have been linked to Rothmund-Thomson syndrome, which is characterized by genome instability, cancer susceptibility, and premature aging. To better define the cellular function of the RecQ4 protein, we investigated the subcellular localization of RecQ4 upon treat...

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Published inThe Journal of biological chemistry Vol. 283; no. 43; pp. 29037 - 29044
Main Authors Fan, Wei, Luo, Jianyuan
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 24.10.2008
American Society for Biochemistry and Molecular Biology
Subjects
Cell Nucleus - metabolism
Cell Survival
Chromatin - metabolism
Cytoplasm - metabolism
DNA Damage
DNA Repair
DNA: , Repair, Recombination, and Chromosome Dynamics
Dose-Response Relationship, Radiation
HeLa Cells
Humans
Models, Biological
Nucleotides - metabolism
RecQ Helicases - metabolism
RecQ Helicases - physiology
Subcellular Fractions - metabolism
Ultraviolet Rays
Xeroderma Pigmentosum Group A Protein - metabolism
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Summary:Mutations in the RECQL4 helicase gene have been linked to Rothmund-Thomson syndrome, which is characterized by genome instability, cancer susceptibility, and premature aging. To better define the cellular function of the RecQ4 protein, we investigated the subcellular localization of RecQ4 upon treatment of cells with different DNA-damaging agents including UV irradiation, 4-nitroquinoline 1-oxide, camptothecin, etoposide, hydroxyurea, and H2O2. We found that RecQ4 formed discrete nuclear foci specifically in response to UV irradiation and 4-nitroquinoline 1-oxide. We demonstrated that functional RecQ4 was required for the efficient removal of UV lesions and could rescue UV sensitivity of RecQ4-deficient Rothmund-Thomson syndrome cells. Furthermore, UV treatment also resulted in the colocalization of the nuclear foci formed with RecQ4 and xeroderma pigmentosum group A in human cells. Consistently, RecQ4 could directly interact with xeroderma pigmentosum group A, and this interaction was stimulated by UV irradiation. By fractionating whole cell extracts into cytoplasmic, soluble nuclear, and chromatin-bound fractions, we observed that RecQ4 protein bound more tightly to chromatin upon UV irradiation. Taken together, our findings suggest a role of RecQ4 in the repair of UV-induced DNA damages in human cells.
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An American Federation for Aging Research (AFAR) Research Grant recipient. To whom correspondence should be addressed: Dept. of Cancer Biology, University of Massachusetts Medical School, 422 LRB, 364 Plantation St., Worcester, MA 01605. Fax: 508-856-1310; E-mail: Jianyuan.luo@umassmed.edu.
This work was supported, in whole or in part, by National Institutes of Health Grant R01AG026534 (to J. L.) through the NIA. This work was also supported in part by grants from Worcester Foundation Annual Research Award. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement”in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M801928200