San Filippo Joseph, Sung Patrick, Klein Hannah
Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA.
Annu Rev Biochem. 2008;77:229-57. doi: 10.1146/annurev.biochem.77.061306.125255.
Homologous recombination (HR) serves to eliminate deleterious lesions, such as double-stranded breaks and interstrand crosslinks, from chromosomes. HR is also critical for the preservation of replication forks, for telomere maintenance, and chromosome segregation in meiosis I. As such, HR is indispensable for the maintenance of genome integrity and the avoidance of cancers in humans. The HR reaction is mediated by a conserved class of enzymes termed recombinases. Two recombinases, Rad51 and Dmc1, catalyze the pairing and shuffling of homologous DNA sequences in eukaryotic cells via a filamentous intermediate on ssDNA called the presynaptic filament. The assembly of the presynaptic filament is a rate-limiting process that is enhanced by recombination mediators, such as the breast tumor suppressor BRCA2. HR accessory factors that facilitate other stages of the Rad51- and Dmc1-catalyzed homologous DNA pairing and strand exchange reaction have also been identified. Recent progress on elucidating the mechanisms of action of Rad51 and Dmc1 and their cohorts of ancillary factors is reviewed here.
同源重组（HR）用于消除染色体上的有害损伤，如双链断裂和链间交联。HR对于复制叉的维持、端粒的维护以及减数分裂I中的染色体分离也至关重要。因此，HR对于维持基因组完整性和避免人类患癌是不可或缺的。HR反应由一类保守的酶介导，称为重组酶。两种重组酶，Rad51和Dmc1，通过单链DNA上的丝状中间体（称为突触前细丝）催化真核细胞中同源DNA序列的配对和重排。突触前细丝的组装是一个限速过程，可通过重组介质（如乳腺肿瘤抑制因子BRCA2）得到增强。还发现了促进Rad51和Dmc1催化的同源DNA配对和链交换反应其他阶段的HR辅助因子。本文综述了阐明Rad51和Dmc1及其辅助因子群体作用机制的最新进展。
