New joint publication by the Luke and Ulrich labs on how Rad53 regulates RNase H1, which promotes DNA replication through sites of transcription-replication conflict
Wagner CB, Longaretti M, Sergi SG, Singh N, Tsirkas I, Bento F, Wong RP, Wilkens M, Hamperl S, Butter F, Aharoni A, Ulrich HD, Luke B (2025) Rad53 regulates RNase H1, which promotes DNA replication through sites of transcription-replication conflict.Cell Rep, 44(11):116565. Link
Abstract:
RNA-DNA hybrids and R-loops can lead to extensive DNA damage and loss of genomic integrity if not regulated in a timely manner. Although RNase H1 overexpression is frequently used as a tool to resolve R-loops, the regulation of RNase H1, overexpressed or endogenous, remains poorly characterized. We reveal that in yeast, overexpressed RNase H1 (RNH1) has no effect on gene expression, cell growth, or RNA-DNA hybrid resolution in wild-type cells. Overexpressed RNase H1 does, however, remove RNA-DNA hybrids in mutants where hybrids have become dysregulated. Endogenous RNase H1 becomes up-regulated and chromatin-associated in the absence of Sen1 in a DNA replication checkpoint-dependent manner. Rnh1 gets recruited to genomic loci where RNA-DNA hybrids accumulate following the loss of Sen1. Rnh1, together with Sen1, promotes DNA replication at sites of transcription-replication conflict. Hence, RNase H1, overexpressed or endogenous, responds to unscheduled, stress-inducing RNA-DNA hybrids.
Read the full paper here: https://www.sciencedirect.com/science/article/pii/S2211124725013373?via%3Dihub
