循环细胞在 S 期通过称为复制计时的定义时间程序复制其 DNA。对于在 S 期早期和晚期复制的基因组区域，突变频率、表观遗传染色质状态和转录活性是不同的。在这里，我们通过 ChIP-Seq 分析发现 DNA 聚合酶 (Pol) κ 在 HEK293T 细胞的早期复制基因组区域中富集。此外，通过给细胞喂食 N 2-庚炔基-2'-脱氧鸟苷，然后进行基于点击化学的富集和高通量测序，我们观察到在 S 期早期复制的基因组区域中 Pol κ 活性升高。基于 Pol κ 在与内源性诱导的 N 2 修饰的 dG 损伤相对的准确有效的核苷酸插入中的既定功能，我们的工作表明 Pol κ 的主动参与可能有助于降低在人类早期复制区域中观察到的突变率基因组，包括癌症基因组。总之，我们的工作扩展了 Pol κ 的功能，并提供了人类基因组中复制时间依赖性突变累积的合理机制。

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.