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

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 Saccharomyces 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).

An Expansion of the Endoplasmic Reticulum that Halts Autophagy is Permissive to Genome Instability.

The links between autophagy and genome stability, and whether they are important for lifespan and health, are not fully understood. We undertook a study to explore this notion at the molecular level using . On the one hand, we triggered autophagy using rapamycin, to which we exposed mutants defective in preserving genome integrity, then assessed their viability, their ability to induce autophagy and the link between these two parameters.

Oxidative agents elicit endoplasmic reticulum morphological changes suggestive of alterations in lipid metabolism.

The endoplasmic reticulum (ER) is a central organelle in charge of correct protein folding; lipids synthesis, modification, and sorting; as well as of maintenance of calcium homeostasis. To accomplish these functions, the ER lumen possesses an oxidative potential. Challenging cells with reductive agents therefore provokes an ER stress that immediately affects protein folding, and which morphologically manifests by an expansion of the cytoplasmic ER network.