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BRCA1 modulates ionizing radiation‐induced nuclear focus formation by the replication protein A p34 subunit
Author(s) -
Choudhary Shailesh K.,
Li Rong
Publication year - 2002
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10081
Subject(s) - dna repair , replication protein a , dna damage , biology , nuclear protein , microbiology and biotechnology , dna replication , protein subunit , dna , ionizing radiation , dna binding protein , genetics , irradiation , gene , transcription factor , physics , nuclear physics
Mutations in BRCA1 account for a significant proportion of familial breast and ovarian cancers. BRCA1 has been implicated in DNA damage responses including double‐strand break (DSB) repair. However, its exact role in DSB repair and its functional relationship with other known repair proteins remain to be elucidated. In this study, we carried out a cytological analysis of the effect of BRCA1 on damage‐induced nuclear focus formation mediated by the replication protein A (RPA). RPA is a multi‐functional protein that participates in both DNA replication and various types of DNA repair including DSB repair. Following ionizing radiation (IR), RPA and BRCA1 formed punctate nuclear staining patterns that co‐localized with each other, consistent with the implicated roles of both proteins in the same repair process. The number of damage‐induced RPA foci in BRCA1‐deficient cells, however, was significantly greater than that in BRCA1‐positive cells. Moreover, the effect of BRCA1 on the RPA staining pattern appeared to be specific for IR but not ultraviolet (UV) irradiation. These data suggest that BRCA1 plays an important role in processing the RPA‐associated intermediates during DSB repair. J. Cell. Biochem. 84: 666–674, 2002. © 2001 Wiley‐Liss, Inc.