Human DNA helicase HELQ participates in DNA interstrand crosslink tolerance with ATR and RAD51 paralogs.
Nat Commun
; 4: 2338, 2013.
Article
em En
| MEDLINE
| ID: mdl-24005565
ABSTRACT
Mammalian HELQ is a 3'-5' DNA helicase with strand displacement activity. Here we show that HELQ participates in a pathway of resistance to DNA interstrand crosslinks (ICLs). Genetic disruption of HELQ in human cells enhances cellular sensitivity and chromosome radial formation by the ICL-inducing agent mitomycin C (MMC). A significant fraction of MMC sensitivity is independent of the Fanconi anaemia pathway. Sister chromatid exchange frequency and sensitivity to UV radiation or topoisomerase inhibitors is unaltered. Proteomic analysis reveals that HELQ is associated with the RAD51 paralogs RAD51B/C/D and XRCC2, and with the DNA damage-responsive kinase ATR. After treatment with MMC, reduced phosphorylation of the ATR substrate CHK1 occurs in HELQ-knockout cells, and accumulation of G2/M cells is reduced. The results indicate that HELQ operates in an arm of DNA repair and signalling in response to ICL. Further, the association with RAD51 paralogs suggests HELQ as a candidate ovarian cancer gene.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
DNA
/
Homologia de Sequência de Aminoácidos
/
DNA Helicases
/
Reagentes de Ligações Cruzadas
/
Rad51 Recombinase
Limite:
Female
/
Humans
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos