生物谷報(bào)道：一個(gè)細(xì)胞中的單鏈DNA非常容易降解,，所以細(xì)胞通過用單鏈DNA結(jié)合蛋白（SSBs）將單鏈DNA覆蓋的辦法,，來將其與核酸酶屏蔽開來。在真核細(xì)胞中,，標(biāo)準(zhǔn)的SSB是一個(gè)異三聚體,，被稱為RPA。在這項(xiàng)研究工作中,，Khanna及其同事發(fā)現(xiàn)了來自人體細(xì)胞的第二種SSB,，他們將其稱為 hSSB1。與RPA不同的是,，hSSB1是一個(gè)單一蛋白,，其主要功能似乎是在細(xì)胞對(duì)DNA損傷的反應(yīng)中,。
生物谷推薦英文原文：
Nature 453, 677-681 (29 May 2008) | doi:10.1038/nature06883; Received 21 December 2007; Accepted 3 March 2008; Published online 30 April 2008
Single-stranded DNA-binding protein hSSB1 is critical for genomic stability
Derek J. Richard1, Emma Bolderson1, Liza Cubeddu2,3, Ross I. M. Wadsworth2, Kienan Savage1,4, Girdhar G. Sharma5, Matthew L. Nicolette6, Sergie Tsvetanov1, Michael J. McIlwraith7, Raj K. Pandita5, Shunichi Takeda8, Ronald T. Hay9, Jean Gautier10, Stephen C. West7, Tanya T. Paull6, Tej K. Pandita5, Malcolm F. White2 & Kum Kum Khanna1
Signal Transduction Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland 4029, Australia
Centre for Biomolecular Sciences, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UK
School of Molecular and Microbial Biosciences, University of Sydney, Sydney, New South Wales 2006, Australia
Central Clinical Division, School of Medicine, University of Queensland, Queensland 4072, Australia
Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri 63108, USA
Department of Molecular Genetics and Microbiology, University of Texas at Austin, Austin, Texas 78712, USA
London Research Institute, Clare Hall Laboratories, Cancer Research UK, South Mimms, Hertfordshire EN6 3LD, U.K
Department of Radiation Genetics, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan
Division of Gene Regulation and Expression, Wellcome Biocentre, University of Dundee, Dundee DD1 5EH, U.K
Institute for Cancer Genetics, Columbia University Medical Center, New York, New York 10032, USA
Correspondence to: Malcolm F. White2Kum Kum Khanna1 Correspondence and requests for materials should be addressed to K.K.K. (Email: [email protected]) or M.F.W. (Email: [email protected]).
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Single-strand DNA (ssDNA)-binding proteins (SSBs) are ubiquitous and essential for a wide variety of DNA metabolic processes, including DNA replication, recombination, DNA damage detection and repair1. SSBs have multiple roles in binding and sequestering ssDNA, detecting DNA damage, stimulating nucleases, helicases and strand-exchange proteins, activating transcription and mediating protein–protein interactions. In eukaryotes, the major SSB, replication protein A (RPA), is a heterotrimer1. Here we describe a second human SSB (hSSB1), with a domain organization closer to the archaeal SSB than to RPA. Ataxia telangiectasia mutated (ATM) kinase phosphorylates hSSB1 in response to DNA double-strand breaks (DSBs). This phosphorylation event is required for DNA damage-induced stabilization of hSSB1. Upon induction of DNA damage, hSSB1 accumulates in the nucleus and forms distinct foci independent of cell-cycle phase. These foci co-localize with other known repair proteins. In contrast to RPA, hSSB1 does not localize to replication foci in S-phase cells and hSSB1 deficiency does not influence S-phase progression. Depletion of hSSB1 abrogates the cellular response to DSBs, including activation of ATM and phosphorylation of ATM targets after ionizing radiation. Cells deficient in hSSB1 exhibit increased radiosensitivity, defective checkpoint activation and enhanced genomic instability coupled with a diminished capacity for DNA repair. These findings establish that hSSB1 influences diverse endpoints in the cellular DNA damage response.
