title: Inviability of a DNA2 deletion mutant is due to the DNA damage checkpoint.
abstract: Dna2 is a dual polarity exo/endonuclease, and 5' to 3' DNA helicase involved in Okazaki Fragment Processing (OFP) and Double-Strand Break (DSB) Repair. In yeast, DNA2 is an essential gene, as expected for a DNA replication protein. Suppression of the lethality of dna2Δ mutants has been found to occur by two mechanisms: overexpression of RAD27 (scFEN1) , encoding a 5' to 3' exo/endo nuclease that processes Okazaki fragments (OFs) for ligation, or deletion of PIF1, a 5' to 3' helicase involved in mitochondrial recombination, telomerase inhibition and OFP. Mapping of a novel, spontaneously arising suppressor of dna2Δ now reveals that mutation of rad9 and double mutation of rad9 mrc1 can also suppress the lethality of dna2Δ mutants. Interaction of dna2Δ and DNA damage checkpoint mutations provides insight as to why dna2Δ is lethal but rad27Δ is not, even though evidence shows that Rad27 (ScFEN1) processes most of the Okazaki fragments, while Dna2 processes only a subset.
authors.affiliation: California Institute of Technology, Pasadena, CA USA.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Budd
authors.forename: Igor A
authors.initials: IA
authors.lastname: Antoshechkin
authors.forename: Clara
authors.initials: C
authors.lastname: Reis
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Wold
authors.forename: Judith L
authors.initials: JL
authors.lastname: Campbell
mesh_terms: D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004265:DNA Helicases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair; D045585:Flap Endonucleases / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D005804:Genes, Lethal; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C022262:Okazaki fragments; D029701:Saccharomyces cerevisiae Proteins; C069930:rad9 protein; D004247:DNA; D019098:Telomerase; D045585:Flap Endonucleases; C468323:RAD27 protein, S cerevisiae; C085463:PIF1 protein, S cerevisiae; D004265:DNA Helicases; C410222:DNA2 protein, S cerevisiae