Chen J J, Silver D, Cantor S, Livingston D M, Scully R
The Dana-Faber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA.
Cancer Res. 1999 Apr 1;59(7 Suppl):1752s-1756s.
The two major hereditary breast cancer susceptibility genes, BRCA1 and BRCA2, are associated with early-onset breast and/or ovarian cancer and encode products that each interact with the product of the eukaryotic RecA homologue, hRad51. We have recently found that BRCA1 and BRCA2 coexist in a common biochemical complex. The two proteins also colocalize in subnuclear foci in somatic cells as well as on the axial elements of developing synaptonemal complexes in meiotic cells. Thus, BRCA1 and BRCA2 participate in a common DNA damage response pathway associated with the activation of homologous recombination and double-strand break repair. Dysfunction of this pathway may be a general phenomenon in the majority of cases of hereditary breast and/or ovarian cancer. The BRCA1/BRCA2 complex may function in postreplicational repair processes activated during the DNA synthesis stage of the cell cycle.
两个主要的遗传性乳腺癌易感基因BRCA1和BRCA2，与早发性乳腺癌和/或卵巢癌相关，并且编码的产物各自与真核生物RecA同源物hRad51的产物相互作用。我们最近发现BRCA1和BRCA2共存于一个共同的生化复合物中。这两种蛋白质还在体细胞的亚核灶中以及减数分裂细胞中发育中的联会复合体的轴向元件上共定位。因此，BRCA1和BRCA2参与了与同源重组激活和双链断裂修复相关的共同DNA损伤反应途径。在大多数遗传性乳腺癌和/或卵巢癌病例中，该途径的功能障碍可能是一种普遍现象。BRCA1/BRCA2复合物可能在细胞周期DNA合成阶段激活的复制后修复过程中发挥作用。
