DNA polymerase κ participates in early S- phase DNA replication in human cells
成果类型：
Article
署名作者：
Tang, Feng; Wang, Yinan; Zhao, Ting; Yuan, Jun; Wang, Yinsheng
署名单位：
University of California System; University of California Riverside; University of California System; University of California Riverside
刊物名称：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN/ISSBN：
0027-10240
DOI：
10.1073/pnas.2405473121
发表日期：
2024-07-09
关键词：
摘要：
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) kappa 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 kappa activities in genomic regions that are replicated early in the S phase. On the basis of the established functions of Pol kappa in accurate and efficient nucleotide insertion opposite endogenously induced N 2- modified dG lesions, our work suggests that active engagement of Pol kappa 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 kappa and offered a plausible mechanism underlying replication timing-dependent mutation accrual in the human genome.