Abstract
Unrepaired DNA lesions in the template strand block the replication fork. In yeast, Mec1 protein kinase-mediated replication checkpoint prevents the breakdown of replication forks and maintains viability in DNA-damaged cells going through the S phase. By ensuring that the replisome does not dissociate from the fork stalled at the lesion site, the replication checkpoint presumably coordinates the action of lesion bypass processes with the replisome. However, it has remained unclear as to which of the lesion bypass processes - translesion synthesis (TLS) and/or template switching - depend on the activation of the replication checkpoint. Here we determine if the Mec1 kinase and the subunits of the checkpoint clamp and the clamp loader are required for TLS. We show that proficient TLS can occur in the absence of these checkpoint proteins in nucleotide excision repair (NER)-proficient cells; however, in the absence of NER, checkpoint protein-mediated Rev1 phosphorylation contributes to increasing the proficiency of DNA polymerase ζ-dependent TLS.
Original language | English (US) |
---|---|
Pages (from-to) | 1438-1449 |
Number of pages | 12 |
Journal | Genes and Development |
Volume | 23 |
Issue number | 12 |
DOIs | |
State | Published - Jun 15 2009 |
Keywords
- DNA damage
- Lesion bypass
- Mec1 kinase Rev1 phosphorylation
- Replication checkpoint
- Translesion synthesis
ASJC Scopus subject areas
- General Medicine