Strand- and replication timing-dependent functions of DNA polymerase η in human DNA replication and mutagenesis [ChIP-Seq]

Under moderate doses of UV, Pol η usage retained its replicative strand bias, which contrasted with the prominent strand bias observed in transcribed regions resulting from asymmetric repair processes. These results reveal that Pol η′s flexibility and intrinsic coupling with replication forks extend beyond TLS in human cells. In cancer genomes, characteristic Pol η mutations are enriched in late-replicating regions and correlate with RAD18 expression, implicating PCNA-mediated Pol η activation in mutagenesis.

Together, these findings reveal an unexpected bias in Pol η usage during unperturbed replication which may represent a key contribution to the mutational burden in the human genome.