Mao Zhiyong, Seluanov Andrei, Jiang Ying, Gorbunova Vera
Department of Biology, University of Rochester, Rochester, NY 14627-0211, USA.
Proc Natl Acad Sci U S A. 2007 Aug 7;104(32):13068-73. doi: 10.1073/pnas.0702410104. Epub 2007 Aug 1.
TRF2 (telomeric repeat binding factor 2) is an essential component of the telomeric cap, where it forms and stabilizes the T-loop junctions. TRF2 forms the T-loops by stimulating strand invasion of the 3' overhang into duplex DNA. TRF2 also has been shown to localize to nontelomeric DNA double-strand breaks, but its functional role in DNA repair has not been examined. Here, we present evidence that TRF2 is involved in homologous recombination (HR) repair of nontelomeric double-strand breaks. Depletion of TRF2 strongly inhibited HR and delayed the formation of Rad51 foci after gamma-irradiation, whereas overexpression of TRF2 stimulated HR. Depletion of TRF2 had no effect on nonhomologous end-joining, and overexpression of TRF2 inhibited nonhomologous end-joining. We propose, based on our results and on the ability of TRF2 to mediate strand invasion, that TRF2 plays an essential role in HR by facilitating the formation of early recombination intermediates.
端粒重复结合因子2（TRF2）是端粒帽的重要组成部分，在端粒帽中它形成并稳定T环连接。TRF2通过刺激3'端突出链侵入双链DNA形成T环。TRF2也已被证明定位于非端粒DNA双链断裂处，但其在DNA修复中的功能作用尚未得到研究。在此，我们提供证据表明TRF2参与非端粒双链断裂的同源重组（HR）修复。TRF2的缺失强烈抑制HR，并延迟γ射线照射后Rad51焦点的形成，而TRF2的过表达则刺激HR。TRF2的缺失对非同源末端连接没有影响，而TRF2过表达则抑制非同源末端连接。基于我们的结果以及TRF2介导链侵入的能力，我们提出TRF2通过促进早期重组中间体的形成在HR中发挥重要作用。
