DNA polymerase κ participates in early S-phase DNA replication in human cells.
| Autor: | Tang F; Department of Chemistry, University of California Riverside, Riverside, CA 92521-0403., Wang Y; Department of Chemistry, University of California Riverside, Riverside, CA 92521-0403., Zhao T; Environmental Toxicology Graduate Program, University of California Riverside, Riverside, CA 92521-0403., Yuan J; Department of Chemistry, University of California Riverside, Riverside, CA 92521-0403., Kellum AH Jr; Department of Chemistry, University of California Riverside, Riverside, CA 92521-0403., Wang Y; Department of Chemistry, University of California Riverside, Riverside, CA 92521-0403.; Environmental Toxicology Graduate Program, University of California Riverside, Riverside, CA 92521-0403. |
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| Jazyk: | angličtina |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Jul 09; Vol. 121 (28), pp. e2405473121. Date of Electronic Publication: 2024 Jul 01. |
| DOI: | 10.1073/pnas.2405473121 |
| Abstrakt: | 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. Competing Interests: Competing interests statement:The authors declare no competing interest. |
| Databáze: | MEDLINE |
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