Abstract
One of the main mechanisms for double stranded DNA break (DSB) repair is through the non-homologous end-joining (NHEJ) pathway. Using plasmid and chromosomal repair assays, we showed that deletion mutant strains for interacting proteins Pph3p and Psy2p had reduced efficiencies in NHEJ. We further observed that this activity of Pph3p and Psy2p appeared linked to cell cycle Rad53p and Chk1p checkpoint proteins. Pph3/Psy2 is a phosphatase complex, which regulates recovery from the Rad53p DNA damage checkpoint. Overexpression of Chk1p checkpoint protein in a parallel pathway to Rad53p compensated for the deletion of PPH3 or PSY2 in a chromosomal repair assay. Double mutant strains Δpph3/Δchk1 and Δpsy2/Δchk1 showed additional reductions in the efficiency of plasmid repair, compared to both single deletions which is in agreement with the activity of Pph3p and Psy2p in a parallel pathway to Chk1p. Genetic interaction analyses also supported a role for Pph3p and Psy2p in DNA damage repair, the NHEJ pathway, as well as cell cycle progression. Collectively, we report that the activity of Pph3p and Psy2p further connects NHEJ repair to cell cycle progression.
Highlights
Among DNA lesions, double-stranded DNA breaks (DSBs) are regarded as the most severe form of DNA damage
The mechanisms for DSB repair are divided in two independent pathways, Homologous Recombination (HR), and Non-Homologous End Joining (NHEJ)
The DNA damage (DD) array was generated on the basis of GO term by arraying gene deletion mutants for 384 genes with known or potential involvement in DNA damage response, DNA replication, cell cycle progression or localization in nucleus
Summary
Among DNA lesions, double-stranded DNA breaks (DSBs) are regarded as the most severe form of DNA damage. The mechanisms for DSB repair are divided in two independent pathways, Homologous Recombination (HR), and Non-Homologous End Joining (NHEJ). HR utilizes an undamaged homologous template, preferably the sister chromatid or homologous chromosomes, to repair the broken sites of DSBs [1], [2], and is considered to be an error free repair pathway [3]. A more flexible alternative to the HR repair system is NHEJ [4], [5]. In NHEJ, the two broken strands of DNA can be ligated directly. Because NHEJ does not use a homologous template, there is a higher risk of errors in repair, which can result in mutations [6]. NHEJ is the main pathway to repair DSBs in mammals [7]
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