细胞具有复杂的调控和修复DNA损伤的复杂系统，但研究人员一直不清楚DNA初始的损伤信号如何实现修复应答的过程。
最近索尔克生物研究所的研究人员解决了这个重要的生物学难题，在一篇发表于12月24日出版的Molecular Cell杂志的研究报告中，他们表明，一种命名为CtIP的蛋白质在DNA损伤后的“信号-修复”的转换过程中起关键作用。
由于CtIP蛋白在酵母细胞中参与DNA损伤末端的修复过程，并且人类DNA发生损伤时该蛋白也出现在损伤位点，因此该课题组想了解CtIP蛋白在人类细胞的功能与酵母细胞中的功能是否相似。课题组使人类细胞CtIP蛋白耗尽并使DNA发生损伤。研究人员发现，当缺失CtIP蛋白质，细胞中DNA的修复过程将被中断。
为了更好地了解CtIP蛋白如何参与DNA的修复过程，以及CtIP蛋白的哪一个区域结合到DNA的损伤末端，研究人员对该蛋白的每个结构域进行测试，他们发现，CtIP蛋白的中心区域可结合到DNA损伤位点。他们将这部分区域命名为“damage recruitment(DR)”结构域。
进一步研究表明，DR结构域通常情况下隐藏在CtIP折叠蛋白的内部，只有当细胞将DNA损伤信号传递到CtIP的DR结构域并且DR结构域暴露出来，CtIP才能与DNA损伤位点结合，从而引发一系列的DNA修复反应。（生物谷Bioon.com）
生物谷推荐原始出处：
Molecular Cell, 24 December 2009 doi:10.1016/j.molcel.2009.12.002
CtIP Links DNA Double-Strand Break Sensing to Resection
Zhongsheng You1, 2, , , Linda Z. Shi4, Quan Zhu3, Peng Wu1, You-Wei Zhang2, 6, Andrew Basilio4, Nina Tonnu3, Inder M. Verma3, Michael W. Berns4, 5 and Tony Hunter2, ,
1 Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA
2 Molecular and Cell Biology Laboratory, The Salk Institute, La Jolla, CA 92037, USA
3 Laboratory of Genetics, The Salk Institute, La Jolla, CA 92037, USA
4 Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA
5 Beckman Laser Institute and Department of Biomedical Engineering, University of California, Irvine, Irvine, CA 92715, USA
In response to DNA double-strand breaks (DSBs), cells sense the DNA lesions and then activate the protein kinase ATM. Subsequent DSB resection produces RPA-coated ssDNA that is essential for activation of the DNA damage checkpoint and DNA repair by homologous recombination (HR). However, the biochemical mechanism underlying the transition from DSB sensing to resection remains unclear. Using Xenopus egg extracts and human cells, we show that the tumor suppressor protein CtIP plays a critical role in this transition. We find that CtIP translocates to DSBs, a process dependent on the DSB sensor complex Mre11-Rad50-NBS1, the kinase activity of ATM, and a direct DNA-binding motif in CtIP, and then promotes DSB resection. Thus, CtIP facilitates the transition from DSB sensing to processing: it does so by binding to the DNA at DSBs after DSB sensing and ATM activation and then promoting DNA resection, leading to checkpoint activation and HR.
