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.

Základní údaje

Originální název

SAMHD1 acts at stalled replication forks to prevent interferon induction

Autoři

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 43.070

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/18:00101770

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

SAMHD1

Štítky

14110513, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 11. 3. 2019 10:41, Soňa Böhmová

Anotace

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.

Návaznosti

GA13-26629S, projekt VaV

Název: SUMO a stability genomu

Investor: Grantová agentura ČR, SUMO a stability genomu

GA17-17720S, projekt VaV

Název: Vnitřní vlastnosti RAD51 vlákna a jeho biologické regulace

Investor: Grantová agentura ČR, Vnitřní vlastnosti RAD51 vlákna a jeho biologické regulace

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 a Philippe PASERO. SAMHD1 acts at stalled replication forks to prevent interferon induction. Nature. LONDON: NATURE PUBLISHING GROUP, 2018, roč. 557, č. 7703, s. "57"-"+", 26 s. ISSN 0028-0836. Dostupné z: https://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 = {https://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 a Philippe PASERO. SAMHD1 acts at stalled replication forks to prevent interferon induction. \textit{Nature}. LONDON: NATURE PUBLISHING GROUP, 2018, roč.~557, č.~7703, s.~''57''-''+'', 26 s. ISSN~0028-0836. Dostupné z: https://doi.org/10.1038/s41586-018-0050-1.

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