The Fanconi anemia protein, FANCG, binds to the ERCC1-XPF endonuclease via its tetratricopeptide repeats and the central domain of ERCC1.
The Fanconi anemia protein, FANCG, binds to the ERCC1-XPF endonuclease via its tetratricopeptide repeats and the central domain of ERCC1.
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DOI：
10.1021/bi100584c
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发表时间：
2010-07-06
期刊：
影响因子：
2.9
通讯作者：
Lambert, Muriel W.
中科院分区：
文献类型：
--
作者：
Wang, Chuan;Lambert, Muriel W.
有证据表明范可尼贫血（FA）蛋白在DNA链间交联（ICL）修复中起重要作用，但其发生的确切机制尚不清楚。ICL修复过程中的关键步骤之一涉及通过在ICL两侧的一条链上的切口将交联从DNA上脱钩并随后将其去除。ERCC 1-XPF内切核酸酶参与该脱钩步骤和交联的去除。我们以前已经表明，需要几个FA蛋白的ERCC 1-XPF在ICLs的网站创建的切口的生产。为了更清楚地建立FA蛋白与ERCC 1-XPF介导的切割步骤之间的联系，进行酵母双杂交分析以确定FANCA、FANCC、FANCF和FANCG是否与ERCC 1和XPF直接相互作用，如果是，则确定相互作用的位点。发现这些FA蛋白之一FANCG对ERCC 1具有强亲和力，对XPF具有中等亲和力。FANCG已被证明含有七个四方三肽重复（TPR）基序，这是介导蛋白质-蛋白质相互作用的基序。使用定点诱变对FANCG与ERCC 1相互作用的位点进行作图，证明FANCG与ERCC 1结合需要TPRs 1、3、5和6。ERCC 1，反过来，被证明通过其中央结构域与FANCG相互作用，这是不同于ERCC 1与XPF结合的区域。本发明证明了FANCG和ERCC 1-XPF内切核酸酶之间的结合，结合我们先前的研究，这些研究表明FANCG参与了由ERCC 1-XPF介导的切割步骤，建立了FA蛋白和ICL修复过程的关键脱钩步骤之间的联系。
There is evidence that Fanconi anemia (FA) proteins play an important role in the repair of DNA interstrand cross-links (ICLs), but the precise mechanism by which this occurs is not clear. One of the critical steps in the ICL repair process involves unhooking of the cross-link from DNA by incisions on one strand on either side of the ICL and its subsequent removal. The ERCC1-XPF endonuclease is involved in this unhooking step and in the removal of the cross-link. We have previously shown that several of the FA proteins are needed for production of incisions created by ERCC1-XPF at sites of ICLs. In order to more clearly establish a link between FA proteins and the incision step(s) mediated by ERCC1-XPF, yeast two-hybrid analysis was undertaken to determine whether FANCA, FANCC, FANCF, and FANCG directly interact with ERCC1 and XPF and, if so, to determine the sites of interaction. One of these FA proteins, FANCG, was found to have strong affinity for ERCC1 and moderate affinity for XPF. FANCG has been shown to contain seven tetratricopeptide repeat (TPR) motifs, which are motifs that mediate protein-protein interactions. Mapping the sites of interaction of FANCG with ERCC1, using site-directed mutagenesis, demonstrated that TPRs 1, 3, 5, and 6 are needed for binding of FANCG to ERCC1. ERCC1, in turn, was shown to interact with FANCG via its central domain, which is different from the region of ERCC1 that binds to XPF. The present demonstrated binding between FANCG and the ERCC1-XPF endonuclease, combined with our previous studies which show that FANCG is involved in the incision step mediated by ERCC1-XPF, establishes a link between an FA protein and the critical unhooking step of the ICL repair process.
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影响因子：
16.8
作者：
Hanada, Katsuhiro;Budzowska, Magda;Kanaar, Roland
通讯作者：
Kanaar, Roland
影响因子：
14.9
作者：
Al-Minawi AZ;Lee YF;Håkansson D;Johansson F;Lundin C;Saleh-Gohari N;Schultz N;Jenssen D;Bryant HE;Meuth M;Hinz JM;Helleday T
通讯作者：
Helleday T
DOI：
10.1006/bbrc.1996.6008
发表时间：
1997-01-23
影响因子：
3.1
作者：
Lambert, MW;Tsongalis, GJ;Parrish, DD
通讯作者：
Parrish, DD
DOI：
10.1126/science.1182372
发表时间：
2009-12-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Knipscheer P;Räschle M;Smogorzewska A;Enoiu M;Ho TV;Schärer OD;Elledge SJ;Walter JC
通讯作者：
Walter JC
影响因子：
5.3
作者：
Bhagwat, Nikhil;Olsen, Anna L.;McHugh, Peter J.
通讯作者：
McHugh, Peter J.