HMCES safeguards replication from oxidative stress and ensures error-free repair.
EMBO Rep
; 21(6): e49123, 2020 06 04.
Article
em En
| MEDLINE
| ID: mdl-32307824
ABSTRACT
Replication across oxidative DNA lesions can give rise to mutations that pose a threat to genome integrity. How such lesions, which escape base excision repair, get removed without error during replication remains unknown. Our PCNA-based screen to uncover changes in replisome composition under different replication stress conditions had revealed a previously unknown PCNA-interacting protein, HMCES/C3orf37. Here, we show that HMCES is a critical component of the replication stress response, mainly upon base misincorporation. We further demonstrate that the absence of HMCES imparts resistance to pemetrexed treatment due to error-prone bypass of oxidative damage. Furthermore, based on genetic screening, we show that homologous recombination repair proteins, such as CtIP, BRCA2, BRCA1, and PALB2, are indispensable for the survival of HMCES KO cells. Hence, HMCES, which is the sole member of the SRAP superfamily in higher eukaryotes known so far, acts as a proofreader on replication forks, facilitates resolution of oxidative base damage, and therefore ensures faithful DNA replication.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Reparo do DNA
/
Replicação do DNA
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article