Lack of G1/S control destabilizes the yeast genome via replication stress-induced DSBs and illegitimate recombination

• Published in: Journal of cell science Vol. 131; no. 24
• Main Authors: Krol, Kamil, Antoniuk-Majchrzak, Justyna, Skoneczny, Marek, Sienko, Marzena, Jendrysek, Justyna, Rumienczyk, Izabela, Halas, Agnieszka, Kurlandzka, Anna, Skoneczna, Adrianna
• Format: Journal Article
• Language: English
• Published: England 17.12.2018
• Subjects: Rad51; Genome instability; Aneuploidy; Srs2; Double-strand break; Cell cycle control
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.226480

The protein Swi6 in is a cofactor in two complexes that regulate the transcription of the genes controlling the G1/S transition. It also ensures proper oxidative and cell wall stress responses. Previously, we found that Swi6 was crucial for the survival of genotoxic stress. Here, we show that a lack of Swi6 causes replication stress leading to double-strand break (DSB) formation, inefficient DNA repair and DNA content alterations, resulting in high cell mortality. Comparative genome hybridization experiments revealed that there was a random genome rearrangement in Δ cells, whereas in diploid Δ Δ cells, chromosome V is duplicated. and , which are located on chromosome V and are known multicopy suppressors of Δ phenotypes, partially reverse Δ genome instability when overexpressed. Another gene on chromosome V, , also supports Δ survival, but at a high cost; Rad51-dependent illegitimate recombination in Δ cells appears to connect DSBs, leading to genome rearrangement and preventing cell death.This article has an associated First Person interview with the first author of the paper.