RNase H2 degrades toxic RNA:DNA hybrids behind stalled forks to promote replication restart

ABSTRACT: R-loops represent a major source of replication stress, but the mechanism by which these structures impede fork progression remains unclear. To address this question, we monitored fork progression, arrest, and restart in S. cerevisiae cells lacking RNase H1 and H2, two enzymes responsible for degrading RNA:DNA hybrids. We found that while RNase H-deficient cells could replicate their chromosomes normally under unchallenged growth conditions, their replication was impaired when exposed to hydroxyurea (HU) or methyl methanesulfonate (MMS). Treated cells exhibited increased levels of RNA:DNA hybrids at stalled forks and were unable to generate RPA-coated single-stranded (ssDNA), an important postreplicative intermediate in resuming replication. Similar impairments in nascent DNA resection and

SUBMITTER: Mr. Jonathan Heuzé 

PROVIDER: S-SCDT-10_15252-EMBJ_2022113104 | biostudies-other |

REPOSITORIES: biostudies-other