Skaar Jeffrey R, Richard Derek J, Saraf Anita, Toschi Alfredo, Bolderson Emma, Florens Laurence, Washburn Michael P, Khanna Kum Kum, Pagano Michele
Howard Hughes Medical Institute, New York University Cancer Institute, New York University School of Medicine, New York, NY 10016, USA.
J Cell Biol. 2009 Oct 5;187(1):25-32. doi: 10.1083/jcb.200907026. Epub 2009 Sep 28.
Human SSB1 (single-stranded binding protein 1 [hSSB1]) was recently identified as a part of the ataxia telangiectasia mutated (ATM) signaling pathway. To investigate hSSB1 function, we performed tandem affinity purifications of hSSB1 mutants mimicking the unphosphorylated and ATM-phosphorylated states. Both hSSB1 mutants copurified a subset of Integrator complex subunits and the uncharacterized protein LOC58493/c9orf80 (henceforth minute INTS3/hSSB-associated element [MISE]). The INTS3-MISE-hSSB1 complex plays a key role in ATM activation and RAD51 recruitment to DNA damage foci during the response to genotoxic stresses. These effects on the DNA damage response are caused by the control of hSSB1 transcription via INTS3, demonstrating a new network controlling hSSB1 function.
人类单链结合蛋白1（hSSB1）最近被鉴定为共济失调毛细血管扩张症突变（ATM）信号通路的一部分。为了研究hSSB1的功能，我们对模拟未磷酸化和ATM磷酸化状态的hSSB1突变体进行了串联亲和纯化。两种hSSB1突变体都共纯化了整合子复合体亚基的一个子集以及未表征的蛋白LOC58493/c9orf80（以下简称微小INTS3/hSSB相关元件[MISE]）。INTS3-MISE-hSSB1复合体在对基因毒性应激的反应过程中，在ATM激活和RAD51募集到DNA损伤位点方面发挥关键作用。对DNA损伤反应的这些影响是由INTS3对hSSB1转录的控制引起的，这证明了一个控制hSSB1功能的新网络。
