RAD51 相关蛋白 1（RAD51AP1）通过一个保守基序与减数分裂重组酶 DMC1 相互作用。
RAD51-associated protein 1 (RAD51AP1) interacts with the meiotic recombinase DMC1 through a conserved motif.
机构信息
Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
出版信息
J Biol Chem. 2011 Oct 28;286(43):37328-34. doi: 10.1074/jbc.M111.290015. Epub 2011 Sep 8.
Abstract
Homologous recombination (HR) reactions mediated by the RAD51 recombinase are essential for DNA and replication fork repair, genome stability, and tumor suppression. RAD51-associated protein 1 (RAD51AP1) is an important HR factor that associates with and stimulates the recombinase activity of RAD51. We have recently shown that RAD51AP1 also partners with the meiotic recombinase DMC1, displaying isoform-specific interactions with DMC1. Here, we have characterized the DMC1 interaction site in RAD51AP1 by a series of truncations and point mutations to uncover a highly conserved WVPP motif critical for DMC1 interaction but dispensable for RAD51 association. This RAD51AP1 motif is reminiscent of the FVPP motif in the tumor suppressor protein BRCA2 that mediates DMC1 interaction. These results further implicate RAD51AP1 in meiotic HR via RAD51 and DMC1.
摘要
同源重组 (HR) 反应由 RAD51 重组酶介导，对于 DNA 和复制叉修复、基因组稳定性和肿瘤抑制至关重要。RAD51 相关蛋白 1 (RAD51AP1) 是一种重要的 HR 因子，它与 RAD51 重组酶的活性相关联并刺激其活性。我们最近表明，RAD51AP1 还与减数分裂重组酶 DMC1 相互作用，与 DMC1 显示出具有同工型特异性的相互作用。在这里，我们通过一系列截断和点突变来表征 RAD51AP1 中的 DMC1 相互作用位点，揭示了一个高度保守的 WVPP 基序对于 DMC1 相互作用至关重要，但对于 RAD51 结合是可有可无的。这个 RAD51AP1 基序让人联想到肿瘤抑制蛋白 BRCA2 中的 FVPP 基序，该基序介导 DMC1 的相互作用。这些结果进一步表明 RAD51AP1 通过 RAD51 和 DMC1 参与减数分裂 HR。
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