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Stable Interaction between the Products of the BRCA1 and BRCA2 Tumor Suppressor Genes in Mitotic and Meiotic Cells

作者:Junjie Chen, Daniel P. Silver, Deepika Walpita, Sharon B. Cantor, Adi F. Gazdar, Gail Elizabeth Tomlinson, Fergus J. Couch, Barbara L. Weber, Terry Ashley, David M. Livingston, Ralph Scully · 发表于:Molecular Cell · 年份:1998 · DOI:10.1016/s1097-2765(00)80276-2 · 被引用次数:634 · 研究领域:BRCA gene mutations in cancer、DNA Repair Mechanisms、CRISPR and Genetic Engineering

BRCA1 and BRCA2 account for most cases of familial, early onset breast and/or ovarian cancer and encode products that each interact with hRAD51. Results presented here show that BRCA1 and BRCA2 coexist in a biochemical complex and colocalize in subnuclear foci in somatic cells and on the axial elements of developing synaptonemal complexes. Like BRCA1 and RAD51, BRCA2 relocates to PCNA+ replication sites following exposure of S phase cells to hydroxyurea or UV irradiation. Thus, BRCA1 and BRCA2 participate, together, in a pathway(s) associated with the activation of double-strand break repair and/or homologous recombination. Dysfunction of this pathway may be a general phenomenon in the majority of cases of hereditary breast and/or ovarian cancer.