Minding the gap: the underground functions of BRCA1 and BRCA2 at stalled replication forks.
The hereditary breast and ovarian cancer predisposition genes, BRCA1 and BRCA2, participate in the repair of DNA double strand breaks by homologous recombination. Circumstantial evidence implicates these genes in recombinational responses to DNA polymerase stalling during the S phase of the cell cycle. These responses play a key role in preventing genomic instability and cancer. Here, we review the current literature implicating the BRCA pathway in HR at stalled replication forks and explore the hypothesis that BRCA1 and BRCA2 participate in the recombinational resolution of single stranded DNA lesions termed "daughter strand gaps", generated during replication across a damaged DNA template.
Nagaraju
Ganesh
G
Department of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA.
Scully
Ralph
R
D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics*; D011995:Recombination, Genetic; D016196:S Phase
D019313:BRCA1 Protein; D024682:BRCA2 Protein