title: BRCA1 promotes induction of ssDNA by ionizing radiation.
abstract: The BRCA1 tumor suppressor contributes to the repair of DNA double-strand breaks (DSB) through homologous recombination, but the mechanism is unknown. The rapid accumulation of BRCA1 into nuclear foci in response to induction of DNA breaks suggests that BRCA1 may function in an early step in the repair pathway. We examined the role of BRCA1 in one such early step, the resection of DSBs to generate ssDNA. The appearance of ssDNA in response to ionizing radiation is similar to that of BRCA1 foci formation, suggesting that the two processes are related. Furthermore, BRCA1 colocalizes to ssDNA sites induced by ionizing radiation. Overexpression of BRCA1 causes an increase in cells exhibiting ssDNA induced by ionizing radiation. Mutant BRCA1 that lacks the COOH-terminal BRCT domain also promotes ssDNA but fails to form nuclear foci. Knockdown of BRCA1 expression reduces ssDNA and Rad51 foci formation in response to ionizing radiation. These results indicate that BRCA1 promotes induction of ssDNA in response to ionizing radiation and accumulates at sites of ssDNA.
authors.affiliation: Department of Pathology and Section of Hematology/Oncology, University of Illinois Cancer Center, Chicago, Illinois 60607, USA. schlegel@uic.edu
authors.forename: Brian P
authors.initials: BP
authors.lastname: Schlegel
authors.forename: Francine M
authors.initials: FM
authors.lastname: Jodelka
authors.forename: Rafael
authors.initials: R
authors.lastname: Nunez
mesh_terms: D019313:BRCA1 Protein / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D001940:Breast / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D004277:DNA, Single-Stranded / Q000096:biosynthesis* / Q000528:radiation effects*; D006801:Humans
chemical_list: D019313:BRCA1 Protein; D004277:DNA, Single-Stranded