Recruitment of DNA polymerase eta by FANCD2 in the early response to DNA damage.
Cell Cycle
; 12(5): 803-9, 2013 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-23388460
ABSTRACT
How Fanconi anemia (FA) protein D2 (FANCD2) performs DNA damage repair remains largely elusive. We report here that translesion synthesis DNA polymerase (pol) eta is a novel mediator of FANCD2 function. We found that wild type (wt) FANCD2, not K561R (mt) FANCD2, can interact with pol eta. Upon DNA damage, the interaction of pol eta with FANCD2 occurs earlier than that with PCNA, which is in concert with our finding that FANCD2 monoubiquitination peaks at an earlier time point than that of PCNA monoubiquitination. FANCD2-null FA patient cells (PD20) carrying histone H2B-fused pol eta and wtFANCD2, respectively, show a similar tendency of low Mitomycin C (MMC) sensitivity, while cells transfected with empty vector control or pol eta alone demonstrate a similar high level of MMC sensitivity. It therefore appears that FANCD2 monoubiquitination plays a similar anchor role as histone to bind DNA in regulating pol eta. Collectively, our study indicates that, in the early phase of DNA damage response, FANCD2 plays crucial roles in recruiting pol eta to the sites of DNA damage for repair.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
/
DNA Polimerase Dirigida por DNA
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Proteína do Grupo de Complementação D2 da Anemia de Fanconi
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Cell Cycle
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos