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Stutz, F.

Publications and source records attributed to Stutz, F..

2 recordsLinked to original sources

The mRNA export adaptor Yra1 contributes to DNA double-strand break repair through its C-box domain

Yra1 is an mRNA export adaptor involved in mRNA biogenesis and export in S. cerevisiae. Yra1 overexpression was recently shown to promote accumulation of DNA:RNA hybrids favoring DNA double strand breaks (DSB), cell senescence and telomere shortening, via an unknown mechanism. Yra1 was also identified at an HO-induced DSB and Yra1 depletion causes defects in DSB repair. Previous work from our laboratory showed that Yra1 ubiquitination by Tom1 is important for mRNA export. Interestingly, we found that Yra1 is also ubiquitinated by the SUMO-targeted ubiquitin ligases Slx5-Slx8 implicated in the interaction of irreparable DSB with nuclear pores. Here we show that Yra1 binds an HO-induced irreparable DSB. Importantly, a Yra1 mutant lacking the evolutionarily conserved C-box is not recruited to an HO-induced irreparable DSB and becomes lethal under DSB induction in a HO-cut reparable system. Together, the data provide evidence that Yra1 plays a crucial role in DSB repair via homologous recombination. Unexpectedly, while the Yra1 C-box is essential, Yra1 sumoylation and/or ubiquitination are dispensable in this process.

molecular biology

Pervasive transcription-dependent chromatin remodeling influences the replication initiation program

In Eukaryotic organisms, replication initiation follows a temporal program. Among the parameters that regulate this program in Saccharomyces cerevisiae, chromatin structure has been at the center of attention without considering the contribution of transcription. Here, we revisit the replication initiation program in the light of pervasive transcription. We find that noncoding RNA transcription termination in the vicinity of replication origins or ARS (Autonomously Replicating Sequences) maximizes replication initiation by restricting transcriptional readthrough into ARS. Consistently, high natural nascent transcription correlates with low ARS efficiency and late replication timing. High readthrough transcription is also linked to chromatin features such as high levels of H3K36me3 and deacetylated nucleosomes. Moreover, forcing ARS readthrough transcription promotes these histone modifications. Finally, replication initiation defects induced by increased transcriptional readthrough are partially rescued in the absence of H3K36 methylation. Altogether, these observations indicate that natural pervasive transcription into ARS influences replication initiation through chromatin remodeling.

molecular biology