SAMHD1 acts at stalled replication forks to prevent interferon induction

被引：354

作者：

Coquel, Flavie ^{[1
]}

Silva, Maria-Joao ^{[1
,14
]}

Techer, Herve ^{[2
]}

Zadorozhny, Karina ^{[3
,4
]}

Sharma, Sushma ^{[5
,6
]}

Nieminuszczy, Jadwiga ^{[7
]}

Mettling, Clement ^{[8
]}

Dardillac, Elodie ^{[9
,10
]}

Barthe, Antoine ^{[1
]}

Schmitz, Anne-Lyne ^{[1
]}

Promonet, Alexy ^{[1
]}

Cribier, Alexandra ^{[11
]}

Sarrazin, Amelie ^{[12
]}

Niedzwiedz, Wojciech ^{[7
]}

Lopez, Bernard ^{[9
,10
]}

Costanzo, Vincenzo ^{[1
]}

Krejci, Lumir ^{[3
,4
,13
]}

Chabes, Andrei ^{[5
,6
]}

Benkirane, Monsef ^{[11
]}

Lin, Yea-Lih ^{[1
]}

Pasero, Philippe ^{[1
]}

机构：

[1] Univ Montpellier, Lab Maintien Integr Genome Cours Repl, Inst Genet Humaine, CNRS,Ligue Canc, Montpellier, France

[2] IFOM, Milan, Italy

[3] Masaryk Univ, Dept Biol, Brno, Czech Republic

[4] Masaryk Univ, Natl Ctr Biomol Res, Brno, Czech Republic

[5] Umea Univ, Dept Med Biochem & Biophys, Umea, Sweden

[6] Umea Univ, Lab Mol Infect Med Sweden MIMS, Umea, Sweden

[7] Inst Canc Res, London, England

[8] Univ Montpellier, Inst Genet Humaine, CNRS, Domiciliat Activat Immunitaire & Infect, Montpellier, France

[9] Univ Paris Sud, CNRS, UMR 8200, Villejuif, France

[10] Univ Paris Sud, Inst Cancerol Gustave Roussy, Ligue Canc, Villejuif, France

[11] Univ Montpellier, CNRS, Inst Genet Humaine, Lab Virol Mol, Montpellier, France

[12] Univ Montpellier, CNRS, BioCampus Montpellier, Montpellier, France

[13] St Annes Univ Hosp, Int Clin Res Ctr, Brno, Czech Republic

[14] Peter MacCallum Canc Ctr, East Melbourne, Vic, Australia

来源：

NATURE | 2018年 / 557卷 / 7703期

基金：

英国医学研究理事会; 瑞典研究理事会; 欧洲研究理事会;

关键词：

AICARDI-GOUTIERES SYNDROME; RESTRICTION FACTOR SAMHD1; CYTOSOLIC DNA SENSOR; HIV-1; RESTRICTION; NUCLEASE ACTIVITY; MAMMALIAN-CELLS; END RESECTION; PROTEIN; STABILITY; REPAIR;

D O I：

10.1038/s41586-018-0050-1

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

SAMHD1 was previously characterized as a dNTPase that protects cells from viral infections. Mutations in SAMHD1 are implicated in cancer development and in a severe congenital inflammatory disease known as Aicardi-Goutieres syndrome. The mechanism by which SAMHD1 protects against cancer and chronic inflammation is unknown. Here we show that SAMHD1 promotes degradation of nascent DNA at stalled replication forks in human cell lines by stimulating the exonuclease activity of MRE11. This function activates the ATR-CHK1 checkpoint and allows the forks to restart replication. In SAMHD1-depleted cells, single-stranded DNA fragments are released from stalled forks and accumulate in the cytosol, where they activate the cGAS-STING pathway to induce expression of pro-inflammatory type I interferons. SAMHD1 is thus an important player in the replication stress response, which prevents chronic inflammation by limiting the release of single-stranded DNA from stalled replication forks.

引用

页码：57 / +

页数：26

共 51 条

[1]

Absence of RNase H2 triggers generation of immunogenic micronuclei removed by autophagy [J].

Bartsch, Kareen ;

Knittler, Katharina ;

Borowski, Christopher ;

Rudnik, Soenke ;

Damme, Markus ;

Aden, Konrad ;

Spehlmann, Martina E. ;

Frey, Norbert ;

Saftig, Paul ;

Chalaris, Athena ;

Rabe, Bjoern .

HUMAN MOLECULAR GENETICS, 2017, 26 (20) :3960-3972

[2]

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

[3]

SMARCAL1 catalyzes fork regression and Holliday junction migration to maintain genome stability during DNA replication [J].

Betous, Remy ;

Mason, Aaron C. ;

Rambo, Robert P. ;

Bansbach, Carol E. ;

Badu-Nkansah, Akosua ;

Sirbu, Bianca M. ;

Eichman, Brandt F. ;

Cortez, David .

GENES & DEVELOPMENT, 2012, 26 (02) :151-162

[4]

Replication fork stability confers chemoresistance in BRCA-deficient cells [J].

Chaudhuri, Arnab Ray ;

Callen, Elsa ;

Ding, Xia ;

Gogola, Ewa ;

Duarte, Alexandra A. ;

Lee, Ji-Eun ;

Wong, Nancy ;

Lafarga, Vanessa ;

Calvo, Jennifer A. ;

Panzarino, Nicholas J. ;

John, Sam ;

Day, Amanda ;

Crespo, Anna Vidal ;

Shen, Binghui ;

Starnes, Linda M. ;

de Ruiter, Julian R. ;

Daniel, Jeremy A. ;

Konstantinopoulos, Panagiotis A. ;

Cortez, David ;

Cantor, Sharon B. ;

Fernandez-Capetillo, Oscar ;

Ge, Kai ;

Jonkers, Jos ;

Rottenberg, Sven ;

Sharan, Shyam K. ;

Nussenzweig, Andre .

NATURE, 2016, 535 (7612) :382-+

[5]

SAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to DNA damage [J].

Clifford, Ruth ;

Louis, Tania ;

Robbe, Pauline ;

Ackroyd, Sam ;

Burns, Adam ;

Timbs, Adele T. ;

Colopy, Glen Wright ;

Dreau, Helene ;

Sigaux, Francois ;

Judde, Jean Gabriel ;

Rotger, Margalida ;

Telenti, Amalio ;

Lin, Yea-Lih ;

Pasero, Philippe ;

Maelfait, Jonathan ;

Titsias, Michalis ;

Cohen, Dena R. ;

Henderson, Shirley J. ;

Ross, Mark T. ;

Bentley, David ;

Hillmen, Peter ;

Pettitt, Andrew ;

Rehwinkel, Jan ;

Knight, Samantha J. L. ;

Taylor, Jenny C. ;

Crow, Yanick J. ;

Benkirane, Monsef ;

Schuh, Anna .

BLOOD, 2014, 123 (07) :1021-1031

[6]

Phosphorylation of SAMHD1 by Cyclin A2/CDK1 Regulates Its Restriction Activity toward HIV-1 [J].

Cribier, Alexandra ;

Descours, Benjamin ;

Chaves Valadao, Ana Luiza ;

Laguette, Nadine ;

Benkirane, Monsef .

CELL REPORTS, 2013, 3 (04) :1036-1043

[7]

Aicardi-Goutieres syndrome and the type I interferonopathies [J].

Crow, Yanick J. ;

Manel, Nicolas .

NATURE REVIEWS IMMUNOLOGY, 2015, 15 (07) :429-440

[8]

BRCA1 Accelerates CtIP-Mediated DNA-End Resection [J].

Cruz-Garcia, Andres ;

Lopez-Saavedra, Ana ;

Huertas, Pablo .

CELL REPORTS, 2014, 9 (02) :451-459

[9]

SAMHD1 Promotes DNA End Resection to Facilitate DNA Repair by Homologous Recombination [J].

Daddacha, Waaqo ;

Koyen, Allyson E. ;

Bastien, Amanda J. ;

Head, PamelaSara E. ;

Dhere, Vishal R. ;

Nabeta, Geraldine N. ;

Connolly, Erin C. ;

Werner, Erica ;

Madden, Matthew Z. ;

Daly, Michele B. ;

Minten, Elizabeth V. ;

Whelan, Donna R. ;

Schlafstein, Ashley J. ;

Zhang, Hui ;

Anand, Roopesh ;

Doronio, Christine ;

Withers, Allison E. ;

Shepard, Caitlin ;

Sundaram, Ranjini K. ;

Deng, Xingming ;

Dynan, William S. ;

Wang, Ya ;

Bindra, Ranjit S. ;

Cejka, Petr ;

Rothenberg, Eli ;

Doetsch, Paul W. ;

Kim, Baek ;

Yu, David S. .

CELL REPORTS, 2017, 20 (08) :1921-1935

[10]

The deoxynucleotide triphosphohydrolase SAMHD1 is a major regulator of DNA precursor pools in mammalian cells [J].

Franzolin, Elisa ;

Pontarin, Giovanna ;

Rampazzo, Chiara ;

Miazzi, Cristina ;

Ferraro, Paola ;

Palumbo, Elisa ;

Reichard, Peter ;

Bianchi, Vera .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (35) :14272-14277

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