Positive role of the mammalian TBPIP/HOP2 protein in DMC1-mediated homologous pairing
Positive role of the mammalian TBPIP/HOP2 protein in DMC1-mediated homologous pairing
复制标题
DOI：
10.1074/jbc.m402481200
复制
发表时间：
2004-08-20
影响因子：
4.8
通讯作者：
Yokoyama, S
中科院分区：
文献类型：
--
作者：
Enomoto, R;Kinebuchi, T;Yokoyama, S
在减数分裂中，同源重组优先发生在同源染色体之间，而不是姐妹染色单体之间，这与有丝分裂重组修复的偏好相反。TBPIP/HOP 2蛋白是确保减数分裂期间同源染色体正确配对的因子。在本研究中，我们发现纯化的小鼠TBPIP/HOP 2蛋白在体外刺激减数分裂DMC 1重组酶催化的同源配对。相比之下，TBPIP/HOP 2不刺激通过RAD 51的同源配对，RAD 51是另一种在减数分裂和有丝分裂重组中起作用的同源配对蛋白。TBPIP/HOP 2在DMC 1介导的同源配对中的积极作用仅在TBPIP/HOP 2在同源配对反应开始之前首先结合双链DNA而不是单链DNA时观察到。缺失分析表明，TBPIP/HOP 2的C末端碱性区域是高效DNA结合所需的，也是其同源配对刺激活性所必需的。因此，这些结果表明，TBPIP/HOP 2直接结合到DNA和功能作为DMC 1的激活剂在同源配对步骤在减数分裂。
In meiosis, homologous recombination preferentially occurs between homologous chromosomes rather than between sister chromatids, which is opposite to the bias of mitotic recombinational repair. The TBPIP/HOP2 protein is a factor that ensures the proper pairing of homologous chromosomes during meiosis. In the present study, we found that the purified mouse TBPIP/HOP2 protein stimulated homologous pairing catalyzed by the meiotic DMC1 recombinase in vitro. In contrast, TBPIP/HOP2 did not stimulate homologous pairing by RAD51, which is another homologous pairing protein acting in both meiotic and mitotic recombination. The positive effect of TBPIP/HOP2 in the DMC1-mediated homologous pairing was only observed when TBPIP/HOP2 first binds to double-stranded DNA, not to single-stranded DNA, before the initiation of the homologous pairing reaction. Deletion analyses revealed that the C-terminal basic region of TBPIP/HOP2 is required for efficient DNA binding and is also essential for its homologous pairing stimulation activity. Therefore, these results suggest that TBPIP/HOP2 directly binds to DNA and functions as an activator for DMC1 during the homologous pairing step in meiosis.