SAMHD1 acts at stalled replication forks to prevent interferon
induction

J 2018

SAMHD1 acts at stalled replication forks to prevent interferon induction

COQUEL, Flavie, Maria Joao SILVA, Hervé TECHER, Karina ZADOROZHNY, Sushma SHARMA et. al.

Basic information

Original name

SAMHD1 acts at stalled replication forks to prevent interferon induction

Authors

COQUEL, Flavie (250 France), Maria Joao SILVA (250 France), Hervé TECHER (380 Italy), Karina ZADOROZHNY (203 Czech Republic, belonging to the institution), Sushma SHARMA (752 Sweden), Jadwiga NIEMINUSZCZY (826 United Kingdom of Great Britain and Northern Ireland), Clément METTLING (250 France), Elodie DARDILLAC (250 France), Antoine BARTHE (250 France), Anne Lyne SCHMITZ (250 France), Alexy PROMONET (250 France), Alexandra CRIBIER (250 France), Amélie SARRAZIN (250 France), Wojciech NIEDZWIEDZ (826 United Kingdom of Great Britain and Northern Ireland), Bernard LOPEZ (250 France), Vincenzo COSTANZO (380 Italy), Lumír KREJČÍ (203 Czech Republic, belonging to the institution), Andrei CHABES (752 Sweden), Monsef BENKIRANE (250 France), Lin YEA-LIH (250 France) and Philippe PASERO (250 France, guarantor)

Edition

Nature, LONDON, NATURE PUBLISHING GROUP, 2018, 0028-0836

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 43.070

RIV identification code

RIV/00216224:14110/18:00101770

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1038/s41586-018-0050-1

UT WoS

000431234500029

Keywords in English

SAMHD1

Abstract

V originále

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.

Links

GA13-26629S, research and development project

Name: SUMO a stability genomu

Investor: Czech Science Foundation

GA17-17720S, research and development project

Name: Vnitřní vlastnosti RAD51 vlákna a jeho biologické regulace

Investor: Czech Science Foundation

Citovat

COQUEL, Flavie, Maria Joao SILVA, Hervé TECHER, Karina ZADOROZHNY, Sushma SHARMA, Jadwiga NIEMINUSZCZY, Clément METTLING, Elodie DARDILLAC, Antoine BARTHE, Anne Lyne SCHMITZ, Alexy PROMONET, Alexandra CRIBIER, Amélie SARRAZIN, Wojciech NIEDZWIEDZ, Bernard LOPEZ, Vincenzo COSTANZO, Lumír KREJČÍ, Andrei CHABES, Monsef BENKIRANE, Lin YEA-LIH and Philippe PASERO. SAMHD1 acts at stalled replication forks to prevent interferon induction. Nature. LONDON: NATURE PUBLISHING GROUP, 2018, vol. 557, No 7703, p. "57"-"+", 26 pp. ISSN 0028-0836. Available from: https://dx.doi.org/10.1038/s41586-018-0050-1.

@article{1504937,
   author = {Coquel, Flavie and Silva, Maria Joao and Techer, Hervé and Zadorozhny, Karina and Sharma, Sushma and Nieminuszczy, Jadwiga and Mettling, Clément and Dardillac, Elodie and Barthe, Antoine and Schmitz, Anne Lyne and Promonet, Alexy and Cribier, Alexandra and Sarrazin, Amélie and Niedzwiedz, Wojciech and Lopez, Bernard and Costanzo, Vincenzo and Krejčí, Lumír and Chabes, Andrei and Benkirane, Monsef and YeaandLih, Lin and Pasero, Philippe},
   article_location = {LONDON},
   article_number = {7703},
   doi = {http://dx.doi.org/10.1038/s41586-018-0050-1},
   keywords = {SAMHD1},
   language = {eng},
   issn = {0028-0836},
   journal = {Nature},
   title = {SAMHD1 acts at stalled replication forks to prevent interferon induction},
   volume = {557},
   year = {2018}
}

TY  - JOUR
ID  - 1504937
AU  - Coquel, Flavie - Silva, Maria Joao - Techer, Hervé - Zadorozhny, Karina - Sharma, Sushma - Nieminuszczy, Jadwiga - Mettling, Clément - Dardillac, Elodie - Barthe, Antoine - Schmitz, Anne Lyne - Promonet, Alexy - Cribier, Alexandra - Sarrazin, Amélie - Niedzwiedz, Wojciech - Lopez, Bernard - Costanzo, Vincenzo - Krejčí, Lumír - Chabes, Andrei - Benkirane, Monsef - Yea-Lih, Lin - Pasero, Philippe
PY  - 2018
TI  - SAMHD1 acts at stalled replication forks to prevent interferon induction
JF  - Nature
VL  - 557
IS  - 7703
SP  - "57"-"+"
EP  - "57"-"+"
PB  - NATURE PUBLISHING GROUP
SN  - 00280836
KW  - SAMHD1
N2  - 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.
ER  -

COQUEL, Flavie, Maria Joao SILVA, Hervé TECHER, Karina ZADOROZHNY, Sushma SHARMA, Jadwiga NIEMINUSZCZY, Clément METTLING, Elodie DARDILLAC, Antoine BARTHE, Anne Lyne SCHMITZ, Alexy PROMONET, Alexandra CRIBIER, Amélie SARRAZIN, Wojciech NIEDZWIEDZ, Bernard LOPEZ, Vincenzo COSTANZO, Lumír KREJČÍ, Andrei CHABES, Monsef BENKIRANE, Lin YEA-LIH and Philippe PASERO. SAMHD1 acts at stalled replication forks to prevent interferon induction. \textit{Nature}. LONDON: NATURE PUBLISHING GROUP, 2018, vol.~557, No~7703, p.~''57''-''+'', 26 pp. ISSN~0028-0836. Available from: https://dx.doi.org/10.1038/s41586-018-0050-1.

Detailed Information on Publication Record