Role of swi7H4 mutant allele of DNA polymerase α in the DNA damage checkpoint response.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Alleles* ; DNA Damage* ; Mutation*; DNA Polymerase I/*genetics ; DNA Polymerase I/*metabolism; Checkpoint Kinase 1 ; DNA Repair ; Gene Knockout Techniques ; Mitosis ; Protein Kinases/metabolism ; Schizosaccharomyces/genetics ; Schizosaccharomyces/metabolism ; Schizosaccharomyces pombe Proteins ; Temperature

Besides being a mediator of initiation of DNA replication, DNA polymerase α plays a key role in chromosome maintenance. Swi7H4, a novel temperature sensitive mutant of DNA polymerase α was shown to be defective in transcriptional silencing at the mating type centromere and telomere loci. It is also required for the establishment of chromatin state that can recruit the components of the heterochromatin machinery at these regions. Recently the role of DNA polymerase α in the S-phase alkylation damage response in S. pombe has also been studied. Here we investigate whether defects generated by swi7H4, a mutant allele of DNA polymerase α can activate a checkpoint response. We show that swi7H4 exhibit conditional synthetic lethality with chk1 null mutant and the double mutant of swi7H4 with chk1 deletion aggravate the chromosome segregation defects. More importantly swi7H4 mutant cells delay the mitotic progression at non permissive temperature that is mediated by checkpoint protein kinase Chk1. In addition we show that, in the swi7H4 mutant background, cells accumulate DNA damage at non permissive temperature activating the checkpoint kinase protein Chk1. Further, we observed synthetic lethality between swi7H4 and a number of genes involved in DNA repair pathway at semi permissive temperature. We summarize that defects in swi7H4 mutant results in DNA damage that delay mitosis in a Chk1 dependent manner that also require the damage repair pathway for proper recovery.

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0 (Schizosaccharomyces pombe Proteins)
EC 2.7.- (Protein Kinases)
EC 2.7.11.1 (Checkpoint Kinase 1)
EC 2.7.11.1 (Chk1 protein, S pombe)
EC 2.7.7.7 (DNA Polymerase I)

Date Created: 20150331 Date Completed: 20160315 Latest Revision: 20201209

20250114

PMC4378889

10.1371/journal.pone.0124063

25822347