SAMHD1 Promotes DNA End Resection to Facilitate DNA Repair by Homologous Recombination.
Cell Rep
; 20(8): 1921-1935, 2017 Aug 22.
Article
em En
| MEDLINE
| ID: mdl-28834754
ABSTRACT
DNA double-strand break (DSB) repair by homologous recombination (HR) is initiated by CtIP/MRN-mediated DNA end resection to maintain genome integrity. SAMHD1 is a dNTP triphosphohydrolase, which restricts HIV-1 infection, and mutations are associated with Aicardi-Goutières 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Reparo do DNA por Junção de Extremidades
/
Recombinação Homóloga
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Proteína 1 com Domínio SAM e Domínio HD
Limite:
Humans
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos