The Chromatin Landscape around DNA Double-Strand Breaks in Yeast and Its Influence on DNA Repair Pathway Choice

Abstract

DNA double-strand breaks (DSBs) are harmful DNA lesions, which elicit catastrophic consequences for genome stability if not properly repaired. DSBs can be repaired by either non-homologous end joining (NHEJ) or homologous recombination (HR). The choice between these two pathways depends on which proteins bind to the DSB ends and how their action is regulated. NHEJ initiates with the binding of the Ku complex to the DNA ends, while HR is initiated by the nucleolytic degradation of the 5′-ended DNA strands, which requires several DNA nucleases/helicases and generates single-stranded DNA overhangs. DSB repair occurs within a precisely organized chromatin environment, where the DNA is wrapped around histone octamers to form the nucleosomes. Nucleosomes impose a barrier to the DNA end processing and repair machinery. Chromatin organization around a DSB is modified to allow proper DSB repair either by the removal of entire nucleosomes, thanks to the action of chromatin remodeling factors, or by post-translational modifications of histones, thus increasing chromatin flexibility and the accessibility of repair enzymes to the DNA. Here, we review histone post-translational modifications occurring around a DSB in the yeast Saccharomyces cerevisiae and their role in DSB repair, with particular attention to DSB repair pathway choice.

Unravelling the role of Set2 protein domains in H3K36 methylation in Saccharomyces cerevisiae

“…Histone post-translational modifications are crucial for the regulation of chromatin architecture and gene expression in S. cerevisiae. Despite its relatively simplistic genome compared to higher eukaryotes, S. cerevisiae shares numerous conserved epigenetic mechanisms with more complex organisms (Marino-Ramirez et al 2006;Dahiya et al 2020;Frigerio et al 2023). Histone methylation at lysine residues is particularly a significant modification, modulating transcriptional activation, repression, and DNA repair pathways.…”

Metabolic Engineering of Model Microorganisms for the Production of Xanthophyll

“…S. cerevisiae is currently the most common yeast species used in xanthophyll synthesis. As a conventional yeast, the strict homologous recombination of S. cerevisiae makes the genetic manipulation easier than other non-conventional yeasts [ 149 ]. Meanwhile, S. cerevisiae is the model strain for studying and applying multi-omics dataset mathematic analysis, CRISPR-based genome-scale engineering, GEMs (genome-scale metabolic models)-guided metabolic state prediction, etc.…”

To Erase or Not to Erase: Non-Canonical Catalytic Functions and Non-Catalytic Functions of Members of Histone Lysine Demethylase Families

“…N-terminal histone tails can be dynamically modified by the addition and/or the removal of post-translational modifications, including methylation [1]. Histone methylation is deeply involved in the control of crucial biological processes such as transcription regulation [2], DNA replication [3], and genomic damage signaling and repair [4,5]. For this reason, it is tightly controlled during cellular processes [6] by the coordinated and balanced action of histone methyltransferases and demethylases [7].…”