Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.
Nat Struct Mol Biol. 2011 Jan;18(1):56-60. doi: 10.1038/nsmb.1946. Epub 2010 Dec 12.
The ubiquitously expressed Rad51 recombinase and the meiosis-specific Dmc1 recombinase promote the formation of strand-invasion products (D-loops) between homologous molecules. Strand-invasion products are processed by either the double-strand break repair (DSBR) or synthesis-dependent strand annealing (SDSA) pathway. D-loops destined to be processed by SDSA need to dissociate, producing non-crossovers, and those destined for DSBR should resist dissociation to generate crossovers. The mechanism that channels recombination intermediates into different homologous-recombination pathways is unknown. Here we show that D-loops in a human DMC1-driven reaction are substantially more resistant to dissociation by branch-migration proteins such as RAD54 than those formed by RAD51. We propose that the intrinsic resistance to dissociation of DMC1 strand-invasion intermediates may account for why DMC1 is essential to ensure the proper segregation of chromosomes in meiosis.
普遍表达的 Rad51 重组酶和减数分裂特异性的 Dmc1 重组酶促进同源分子之间链入侵产物（D 环）的形成。链入侵产物通过双链断裂修复（DSBR）或合成依赖性链退火（SDSA）途径进行处理。需要通过 SDSA 进行处理的 D 环需要解离，产生非交叉，而那些注定要通过 DSBR 处理的 D 环应该抵抗解离以产生交叉。将重组中间体引导到不同同源重组途径的机制尚不清楚。在这里，我们表明，在人类 DMC1 驱动的反应中，D 环比由 RAD51 形成的 D 环更能抵抗分支迁移蛋白（如 RAD54）的解离。我们提出，DMC1 链入侵中间体对解离的固有抗性可能解释了为什么 DMC1 对于确保减数分裂中染色体的正确分离是必不可少的。
