ThePSO4 gene is responsible for an error-prone recombinational DNA repair pathway inSaccharomyces cerevisiae

Abstract

The induction of mitotic gene conversion and crossing-over in Saccharomyces cerevisiae diploid cells homozygous for the pso4-1 mutation was examined in comparison to the corresponding wild-type strain. The pso4-1 mutant strain was found to be completely blocked in mitotic recombination induced by photoaddition of mono- and bifunctional psoralen derivatives as well as by mono- (HN1) and bifunctional (HN2) nitrogen mustards or 254 nm UV radiation in both stationary and exponential phases of growth. Concerning the lethal effect, diploids homozygous for the pso4-1 mutation are more sensitive to all agents tested in any growth phase. However, this effect is more pronounced in the G2 phase of the cell cycle. These results imply that the ploidy effect and the resistance of budding cells are under the control of the PSO4 gene. On the other hand, the pso4-1 mutant is mutationally defective for all agents used. Therefore, the pso4-1 mutant has a generalized block in both recombination and mutation ability. This indicates that the PSO4 gene is involved in an error-prone repair pathway which relies on a recombinational mechanism, strongly suggesting an analogy between the pso4-1 mutation and the RecA or LexA mutation of Escherichia coli.

New Faces of old Friends: Emerging new Roles of RNA-Binding Proteins in the DNA Double-Strand Break Response

“…In addition, it has also long been implicated in diverse genome maintenance pathways such as DNA interstrand crosslink-, DSB-and transcription-coupled repair and in the replication stress response (Chanarat and Sträßer, 2013). Indeed, human PRPF19 was first identified in S. cerevisiae as Pso4, whose loss sensitizes yeast to several genotoxins, particularly to DNA interstrand crosslinkinducing agents (Henriques et al, 1989;Rodrigues de Andrade et al, 1989;da Silva et al, 1995;Gray et al, 1996;Revers et al, 2002). In addition, mammalian cells deficient of PRPF19 display a pronounced sensitivity to DSB-inducing agents such as ionizing radiation and etoposide (Mahajan and Mitchell, 2003;Beck et al, 2008;Abbas et al, 2014).…”

The PRP19 Ubiquitin Ligase, Standing at the Cross-Roads of mRNA Processing and Genome Stability

“…Accordingly, xs9 was renamed pso4-1 as it was non-allelic to the other three psoralen-sensitive strains described at the time [ 28 , 29 ]. pso4-1 is also sensitive to UV, nitrogen mustard and methyl methane sulfonate, is hypomutable when exposed to these genotoxins and has impaired mitotic recombination (gene conversion and crossing over) [ 30 , 31 ]. Further mechanistic studies showed that incision at psoralen-induced crosslinks occurred normally in pso4-1 mutants but the recombination-mediated rejoining step was impaired.…”

“…In this regard, it was recently proposed that RFWD3 interacts with and promotes PCNA ubiquitylation to regulate replication fork progression and translesion synthesis [ 118 , 119 , 120 ]. Whether PRP19 also participates in DNA damage tolerance pathways remains an open question but it is interesting that in yeast, Prp19/Pso4 promotes mitotic recombination while also participating in error-prone repair of DNA lesions [ 29 , 30 , 32 ]. Thus, in response to replication stress, the NTC transforms into a sensor of RPA-ssDNA and functions as a ubiquitin ligase to promote ATR signaling and fork repair.…”

The Many Faces of Lipids in Genome Stability (and How to Unmask Them)

“…That a protein can accomplish two different tasks within the cell is no big surprise. Prp19 was first identified as Pso4, a gene required in S. cerevisiae to support error-prone recombinational DNA repair [ 150 ]. This role was later extended to human cells [ 151 , 152 ].…”