Cell biology of cancer: BRCA1 and sister chromatid pairing reactions?
A significant portion of familial breast/ovarian cancer patients harbors a mutation in Breast Cancer Associated gene 1 (BRCA1). Cells deficient for BRCA1 exhibit chromosome aberrations such as whole chromosome duplications, translocations, inter-sister gaps and gene mis-regulation. Here, new evidence is reviewed that defects in sister chromatid cohesion may contribute directly to cancer cell phenotypes-especially those of BRCA1 mutant cells. Linking cohesion to BRCA1-dependent tumorigenesis are reports that BRCA1-associated components (DNA helicase, RFC, PCNA and genome surveillance factors) are required for efficient sister chromatid cohesion. Other cohesion factors (WAPL, EFO2/ESCO2 and hSecurin) are tightly correlated with various cell-type specific carcinogenesis, in support of a generalized model for cohesion in cancer. Recent findings further reveal that a reciprocal relationship exists in that DNA damage induces new Ctf7/Eco1-dependent sister chromatid pairing reactions that, in turn, are required for efficient DNA repair. Future research into sister chromatid pairing mechanisms are likely to provide critical new insights into the underlying causes of cancer.
Skibbens
Robert V
RV
Lehigh University Department of Biological Sciences, Bethlehem, Pennsylvania 18015, USA. rvs3@lehigh.edu
D019313:BRCA1 Protein / Q000172:deficiency* / Q000235:genetics; D001943:Breast Neoplasms / Q000378:metabolism*; D002842:Chromatids / Q000378:metabolism*; D020090:Chromosome Segregation / Q000235:genetics / Q000502:physiology*; D004249:DNA Damage; D005260:Female; D006801:Humans; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D010051:Ovarian Neoplasms / Q000378:metabolism*
D019313:BRCA1 Protein; C492913:BRCA1 protein, human