A RAP1/TRF2 complex inhibits nonhomologous end-joining at human telomeric DNA ends
A RAP1/TRF2 complex inhibits nonhomologous end-joining at human telomeric DNA ends
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DOI：
10.1016/j.molcel.2007.03.023
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发表时间：
2007-05-11
期刊：
影响因子：
16
通讯作者：
Baumann, Peter
中科院分区：
文献类型：
--
作者：
Bae, Nancy S.;Baumann, Peter
端粒与DNA双链断裂的区别机制知之甚少。在这里，我们已经定义了保护端粒DNA末端免受非同源末端连接（NHEJ）的最低要求。无论是长的单链突出端，也不是t环的形成是必不可少的，以防止NHEJ介导的端粒末端在体外连接。相反，12个端粒重复序列的串联阵列足以在附近的DNA末端以高度定向的方式阻止非法修复。末端保护的极性与天然存在的端粒的方向一致，并且非常适合于最小化染色体加帽和亚端粒序列中DNA双链断裂的修复之间的干扰。生化分离和重建显示端粒保护是由RAP 1/TRF 2复合物介导的，为人类RAP 1在保护端粒DNA免受NHEJ损伤中的直接作用提供了证据。
The mechanisms by which telomeres are distinguished from DNA double-strand breaks are poorly understood. Here we have defined the minimal requirements for the protection of telomeric DNA ends from nonhomologous end-joining (NHEJ). Neither long, single-stranded overhangs nor t loop formation is essential to prevent NHEJ-mediated ligation of telomeric ends in vitro. Instead, a tandem array of 12 telomeric repeats is sufficient to impede illegitimate repair in a highly directional manner at nearby DNA ends. The polarity of end protection is consistent with the orientation of naturally occurring telomeres and is well suited to minimize interference between chromosome capping and the repair of DNA double-strand breaks in subtelomeric sequences. Biochemical fractionation and reconstitution revealed that telomere protection is mediated by a RAP1/TRF2 complex, providing evidence for a direct role for human RAP1 in the protection of telomeric DNA from NHEJ.