PARP1 and PARP2 stabilise replication forks at base excision repair intermediates through Fbh1-dependent Rad51 regulation.
Nat Commun
; 9(1): 746, 2018 02 21.
Article
em En
| MEDLINE
| ID: mdl-29467415
ABSTRACT
PARP1 regulates the repair of DNA single-strand breaks generated directly, or during base excision repair (BER). However, the role of PARP2 in these and other repair mechanisms is unknown. Here, we report a requirement for PARP2 in stabilising replication forks that encounter BER intermediates through Fbh1-dependent regulation of Rad51. Whereas PARP2 is dispensable for tolerance of cells to SSBs or homologous recombination dysfunction, it is redundant with PARP1 in BER. Therefore, combined disruption of PARP1 and PARP2 leads to defective BER, resulting in elevated levels of replication-associated DNA damage owing to an inability to stabilise Rad51 at damaged replication forks and prevent uncontrolled DNA resection. Together, our results demonstrate how PARP1 and PARP2 regulate two independent, but intrinsically linked aspects of DNA base damage tolerance by promoting BER directly, and by stabilising replication forks that encounter BER intermediates.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Poli(ADP-Ribose) Polimerases
/
DNA Helicases
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Proteínas de Ligação a DNA
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Reparo do DNA
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Rad51 Recombinase
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Poli(ADP-Ribose) Polimerase-1
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article