SAMHD1 Promotes DNA End Resection to Facilitate DNA Repair by Homologous Recombination

被引：146

作者：

Daddacha, Waaqo ^{[1
,2
]}

Koyen, Allyson E. ^{[1
,2
]}

Bastien, Amanda J. ^{[1
,2
]}

Head, PamelaSara E. ^{[1
,2
]}

Dhere, Vishal R. ^{[1
,2
]}

Nabeta, Geraldine N. ^{[1
,2
]}

Connolly, Erin C. ^{[1
,2
]}

Werner, Erica ^{[1
,2
,3
]}

Madden, Matthew Z. ^{[1
,2
]}

Daly, Michele B. ^{[4
]}

Minten, Elizabeth V. ^{[1
,2
]}

Whelan, Donna R. ^{[5
]}

Schlafstein, Ashley J. ^{[1
,2
]}

Zhang, Hui ^{[1
,2
]}

Anand, Roopesh ^{[6
]}

Doronio, Christine ^{[1
,2
]}

Withers, Allison E. ^{[2
]}

Shepard, Caitlin ^{[4
]}

Sundaram, Ranjini K. ^{[7
]}

Deng, Xingming ^{[1
,2
]}

Dynan, William S. ^{[1
,2
,3
]}

Wang, Ya ^{[1
,2
]}

Bindra, Ranjit S. ^{[7
]}

Cejka, Petr ^{[6
]}

Rothenberg, Eli ^{[5
]}

Doetsch, Paul W. ^{[1
,2
,3
]}

Kim, Baek ^{[4
]}

Yu, David S. ^{[1
,2
]}

机构：

[1] Emory Univ, Sch Med, Dept Radiat Oncol, Atlanta, GA 30322 USA

[2] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA

[3] Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA

[4] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA

[5] NYU, Sch Med, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA

[6] Univ Svizzera Italiana, Inst Res Biomed, Via Vela 6, CH-6500 Bellinzona, Switzerland

[7] Yale Univ, Sch Med, Dept Radiat Oncol, New Haven, CT 06520 USA

来源：

CELL REPORTS | 2017年 / 20卷 / 08期

关键词：

AICARDI-GOUTIERES SYNDROME; REPLICATION STRESS-RESPONSE; RESTRICTION FACTOR SAMHD1; DOUBLE-STRAND BREAKS; DEOXYNUCLEOSIDE TRIPHOSPHATE TRIPHOSPHOHYDROLASE; ACID BINDING-PROTEIN; HIV-1; RESTRICTION; RIBONUCLEASE-ACTIVITY; ENDONUCLEASE ACTIVITY; PANCREATIC-CANCER;

D O I：

10.1016/j.celrep.2017.08.008

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

DNA double-strand break (DSB) repair by homologous recombination (HR) is initiated by CtIP/MRNmediated DNA end resection to maintain genome integrity. SAMHD1 is a dNTP triphosphohydrolase, which restricts HIV-1 infection, and mutations are associated with Aicardi-Goutie` res syndrome and cancer. We show that SAMHD1 has a dNTPase-independent function in promoting DNA end resection to facilitate DSB repair by HR. SAMHD1 deficiency or Vpx-mediated degradation causes hypersensitivity to DSB-inducing agents, and SAMHD1 is recruited to DSBs. SAMHD1 complexes with CtIP via a conserved C-terminal domain and recruits CtIP to DSBs to facilitate end resection and HR. Significantly, a cancer-associated mutant with impaired CtIP interaction, but not dNTPase-inactive SAMHD1, fails to rescue the end resection impairment of SAMHD1 depletion. Our findings define a dNTPase-independent function for SAMHD1 in HR-mediated DSB repair by facilitating CtIP accrual to promote DNA end resection, providing insight into how SAMHD1 promotes genome integrity.

引用

页码：1921 / 1935

页数：15

共 72 条

[1]

Phosphorylated CtIP Functions as a Co-factor of the MRE11-RAD50-NBS1 Endonuclease in DNA End Resection [J].

Anand, Roopesh ;

Ranjha, Lepakshi ;

Cannavo, Elda ;

Cejka, Petr .

MOLECULAR CELL, 2016, 64 (05) :940-950

[2]

SAMHD1-mediated HIV-1 restriction in cells does not involve ribonuclease activity [J].

Antonucci, Jenna M. ;

St Gelais, Corine ;

de Silva, Suresh ;

Yount, Jacob S. ;

Tang, Chenxiang ;

Ji, Xiaoyun ;

Shepard, Caitlin ;

Xiong, Yong ;

Kim, Baek ;

Wu, Li .

NATURE MEDICINE, 2016, 22 (10) :1072-1074

[3]

The HD domain defines a new superfamily of metal-dependent phosphohydrolases [J].

Aravind, L ;

Koonin, EV .

TRENDS IN BIOCHEMICAL SCIENCES, 1998, 23 (12) :469-472

[4]

SAMHD1 restricts HIV-1 infection in resting CD4+ T cells [J].

Baldauf, Hanna-Mari ;

Pan, Xiaoyu ;

Erikson, Elina ;

Schmidt, Sarah ;

Daddacha, Waaqo ;

Burggraf, Manja ;

Schenkova, Kristina ;

Ambiel, Ina ;

Wabnitz, Guido ;

Gramberg, Thomas ;

Panitz, Sylvia ;

Flory, Egbert ;

Landau, Nathaniel R. ;

Sertel, Serkan ;

Rutsch, Frank ;

Lasitschka, Felix ;

Kim, Baek ;

Koenig, Renate ;

Fackler, Oliver T. ;

Keppler, Oliver T. .

NATURE MEDICINE, 2012, 18 (11) :1682-+

[5]

Nuclease Activity of the Human SAMHD1 Protein Implicated in the Aicardi-Goutieres Syndrome and HIV-1 Restriction [J].

Beloglazova, Natalia ;

Flick, Robert ;

Tchigvintsev, Anatoli ;

Brown, Greg ;

Popovic, Ana ;

Nocek, Boguslaw ;

Yakunin, Alexander F. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2013, 288 (12) :8101-8110

[6]

A simple, versatile and efficient method to genetically modify human monocyte-derived dendritic cells with HIV-1-derived lentiviral vectors [J].

Berger, Gregory ;

Durand, Stephanie ;

Goujon, Caroline ;

Xuan-Nhi Nguyen ;

Cordeil, Stephanie ;

Darlix, Jean-Luc ;

Cimarelli, Andrea .

NATURE PROTOCOLS, 2011, 6 (06) :806-816

[7]

Contribution of oligomerization to the anti-HIV-1 properties of SAMHD1 [J].

Brandariz-Nunez, Alberto ;

Valle-Casuso, Jose Carlos ;

White, Tommy E. ;

Nguyen, Laura ;

Bhattacharya, Akash ;

Wang, Zhonghua ;

Demeler, Borries ;

Amie, Sarah ;

Knowlton, Caitlin ;

Kim, Baek ;

Ivanov, Dmitri N. ;

Diaz-Griffero, Felipe .

RETROVIROLOGY, 2013, 10

[8]

Sae2 promotes dsDNA endonuclease activity within Mre11-Rad50-Xrs2 to resect DNA breaks [J].

Cannavo, Elda ;

Cejka, Petr .

NATURE, 2014, 514 (7520) :122-+

[9]

Rmi1 stimulates decatenation of double Holliday junctions during dissolution by Sgs1-Top3 [J].

Cejka, Petr ;

Plank, Jody L. ;

Bachrati, Csanad Z. ;

Hickson, Ian D. ;

Kowalczykowski, Stephen C. .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2010, 17 (11) :1377-U270

[10]

The cBio Cancer Genomics Portal: An Open Platform for Exploring Multidimensional Cancer Genomics Data [J].

Cerami, Ethan ;

Gao, Jianjiong ;

Dogrusoz, Ugur ;

Gross, Benjamin E. ;

Sumer, Selcuk Onur ;

Aksoy, Buelent Arman ;

Jacobsen, Anders ;

Byrne, Caitlin J. ;

Heuer, Michael L. ;

Larsson, Erik ;

Antipin, Yevgeniy ;

Reva, Boris ;

Goldberg, Arthur P. ;

Sander, Chris ;

Schultz, Nikolaus .

CANCER DISCOVERY, 2012, 2 (05) :401-404

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