Identification of different classes of genome instability suppressor genes through analysis of DNA damage response markers

Abstract

Cellular pathways that detect DNA damage are useful for identifying genes that suppress DNA damage, which can cause genome instability and cancer predisposition syndromes when mutated. We identified 199 high-confidence and 530 low-confidence DNA damage suppressing (DDS) genes in Saccharomyces cerevisiae through a whole genome screen for mutations inducing Hug1 expression, a focused screen for mutations inducing Ddc2 foci, and data from previous screens for mutations causing Rad52 foci accumulation and Rnr3 induction. We also identified 286 high-confidence and 394 low-confidence diverse genome instability suppressing (DGIS) genes through a whole genome screen for mutations resulting in increased gross chromosomal rearrangements and data from previous screens for mutations causing increased genome instability as assessed in a diversity of genome instability assays. Genes that suppress both pathways (DDS + DGIS+) prevent or repair DNA replication damage and likely include genes preventing collisions between the replication and transcription machineries. DDS + DGIS- genes, including many transcription-related genes, likely suppress damage that is normally repaired properly or prevent inappropriate signaling, whereas DDS- DGIS + genes, like PIF1, do not suppress damage but likely promote its proper, non-mutagenic repair. Thus, induction of DNA damage markers is not a reliable indicator of increased genome instability, and the DDS and DGIS categories define of mechanistically distinct groups of genes.

The micromammals

“…There is still much to learn about how these common organisms function. Well-done studies on single genes that advance the field always have a home in G3 , and we’ve also seen targeted high-throughput approaches to comprehensively identify new functions or pathways involving known factors ( Lao et al 2018 ; Chatfield-Reed et al 2022 ; Lin et al 2022 ; Li et al 2024 ).…”