两个遗传性乳腺癌易感基因BRCA1 和 BRCA2在对DNA损伤的反应中发挥作用。当它们发生突变或缺失时，就会导致基因组不稳定，这是癌症形成的一个重要因素。
针对BRCA2的研究工作因其分子较大而受阻，因为这会使全长度蛋白的纯化具有挑战性。现在，Steve Kowalczykowski及其同事报告了首次在试管中对全长度BRCA2的定性，并描绘了BRCA2帮助由Rad51-调控的同源重组的不同方式。（生物谷Bioon.com）
生物谷推荐英文摘要：
Nature doi:10.1038/nature09399
Purified human BRCA2 stimulates RAD51-mediated recombination
Ryan B. Jensen,Aura Carreira& Stephen C. Kowalczykowski
Mutation of the breast cancer susceptibility gene, BRCA2, leads to breast and ovarian cancers. Mechanistic insight into the functions of human BRCA2 has been limited by the difficulty of isolating this large protein (3,418 amino acids). Here we report the purification of full-length BRCA2 and show that it both binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). BRCA2 acts by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace replication protein-A (RPA) from ssDNA and stabilizing RAD51–ssDNA filaments by blocking ATP hydrolysis. BRCA2 does not anneal ssDNA complexed with RPA, implying it does not directly function in repair processes that involve ssDNA annealing. Our findings show that BRCA2 is a key mediator of homologous recombination, and they provide a molecular basis for understanding how this DNA repair process is disrupted by BRCA2 mutations, which lead to chromosomal instability and cancer.
