ArticleThe Journal of biological chemistry2009
The MPH1 gene of Saccharomyces cerevisiae functions in Okazaki fragment processing.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 30 citations in OpenAlex.
- The secondary-structured DNA-binding activity of Dna2 endonuclease/helicase is critical to cell growth under replication stress.The FEBS journal · 2021Article
- A Critical Role for Dna2 at Unwound Telomeres.Genetics · 2018Article
- Article
- Avoidance of APOBEC3B-induced mutation by error-free lesion bypass.Nucleic acids research · 2017Article
- Dosage Mutator Genes in Saccharomyces cerevisiae: A Novel Mutator Mode-of-Action of the Mph1 DNA Helicase.Genetics · 2016Article
- Article
- Rad52/Rad59-dependent recombination as a means to rectify faulty Okazaki fragment processing.The Journal of biological chemistry · 2014Article
- Preventing over-resection by DNA2 helicase/nuclease suppresses repair defects in Fanconi anemia cells.Cell cycle (Georgetown, Tex.) · 2014Article
- Roles of DNA helicases in the mediation and regulation of homologous recombination.Advances in experimental medicine and biology · 2013Article
- DNA2 and EXO1 in replication-coupled, homology-directed repair and in the interplay between HDR and the FA/BRCA network.Cell cycle (Georgetown, Tex.) · 2012Article
- Biochemical studies of the Saccharomyces cerevisiae Mph1 helicase on junction-containing DNA structures.Nucleic acids research · 2012Article
- The Mph1 helicase can promote telomere uncapping and premature senescence in budding yeast.PloS one · 2012Article
- Inviability of a DNA2 deletion mutant is due to the DNA damage checkpoint.Cell cycle (Georgetown, Tex.) · 2011Article
- Genetic and functional interactions between Mus81-Mms4 and Rad27.Nucleic acids research · 2010Article
- Mph1 requires mismatch repair-independent and -dependent functions of MutSalpha to regulate crossover formation during homologous recombination repair.Nucleic acids research · 2010Article
- Interplay between the Smc5/6 complex and the Mph1 helicase in recombinational repair.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- Human replication factor C stimulates flap endonuclease 1.The Journal of biological chemistry · 2009Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Saccharomyces cerevisiae MPH1 was first identified as a gene encoding a 3' to 5' DNA helicase, which when deleted leads to a mutator phenotype. In this study, we isolated MPH1 as a multicopy suppressor of the dna2K1080E helicase-negative lethal mutant. Purified Mph1 stimulated the endonuclease activities of both Fen1 and Dna2, which act faithfully in the processing of Okazaki fragments. This stimulation required neither ATP hydrolysis nor the helicase activity of Mph1. Multicopy expression of MPH1 also suppressed the temperature-sensitive growth defects in cells expressing dna2Delta405N, which lacks the N-terminal 405 amino acids of Dna2. However, Mph1 did not stimulate the endonuclease activity of the Dna2Delta405N mutant protein. The stimulation of Fen1 by Mph1 was limited to flap-structured substrates; Mph1 hardly stimulated the 5' to 3' exonuclease activity of Fen1. Mph1 binds to flap-structured substrate more efficiently than to nicked duplex structures, suggesting that the stimulatory effect of Mph1 is exerted through its binding to DNA substrates. In addition, we found that Mph1 reversed the inhibitory effects of replication protein A on Fen1 activity. Our biochemical and genetic data indicate that the in vivo suppression of Dna2 defects observed with both dna2K1080E and dna2Delta405N mutants occur via stimulation of Fen1 activity. These findings suggest that Mph1 plays an important, although not essential, role in processing of Okazaki fragments by facilitating the formation of ligatable nicks.
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