DNA polymerase κ participates in early S-phase DNA replication in human cells.
Proc Natl Acad Sci U S A
; 121(28): e2405473121, 2024 Jul 09.
Article
in En
| MEDLINE
| ID: mdl-38950361
ABSTRACT
Cycling cells replicate their DNA during the S phase through a defined temporal program known as replication timing. Mutation frequencies, epigenetic chromatin states, and transcriptional activities are different for genomic regions that are replicated early and late in the S phase. Here, we found from ChIP-Seq analysis that DNA polymerase (Pol) κ is enriched in early-replicating genomic regions in HEK293T cells. In addition, by feeding cells with N 2-heptynyl-2'-deoxyguanosine followed by click chemistry-based enrichment and high-throughput sequencing, we observed elevated Pol κ activities in genomic regions that are replicated early in the S phase. On the basis of the established functions of Pol κ in accurate and efficient nucleotide insertion opposite endogenously induced N 2-modified dG lesions, our work suggests that active engagement of Pol κ may contribute to diminished mutation rates observed in early-replicating regions of the human genome, including cancer genomes. Together, our work expands the functions of Pol κ and offered a plausible mechanism underlying replication timing-dependent mutation accrual in the human genome.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
S Phase
/
DNA-Directed DNA Polymerase
/
DNA Replication
Limits:
Humans
Language:
En
Journal:
Proc Natl Acad Sci U S A
/
Proc. Natl. Acad. Sci. U. S. A
/
Proceedings of the national academy of sciences of the United States of America
Year:
2024
Type:
Article