Strand- and replication timing-dependent functions of DNA polymerase η in human DNA replication and mutagenesis [Pu-seq].

DNA polymerase η (Pol η) is most recognised for tolerating UV-induced DNA damage via translesion synthesis (TLS). However, emerging evidence suggests a broader contribution of error-prone polymerases to DNA synthesis.

To elucidate the roles of Pol η during unperturbed replication, we applied polymerase usage sequencing (Pu-seq) to map its activity genome-wide in human cells. Our findings demonstrate that Pol η preferentially participates in lagging-strand replication, consistent with observations in budding yeast. Under moderate doses of UV, Pol η usage retains its replicative strand bias, which contrasts with the prominent strand bias observed in transcribed regions resulting from asymmetric repair processes.