Amino acid changes in Xrs2p, Dun1p, and Rfa2p that remove the preferred targets of the ATM family of protein kinases do not affect DNA repair or telomere length in Saccharomyces cerevisiae.

Abstract:

:In eukaryotes, mutations in a number of genes that affect DNA damage checkpoints or DNA replication also affect telomere length [Curr. Opin. Cell Biol. 13 (2001) 281]. Saccharomyces cerevisae strains with mutations in the TEL1 gene (encoding an ATM-like protein kinase) have very short telomeres, as do strains with mutations in XRS2, RAD50, or MRE11 (encoding members of a trimeric complex). Xrs2p and Mre11p are phosphorylated in a Tel1p-dependent manner in response to DNA damage [Genes Dev. 15 (2001) 2238; Mol. Cell 7 (2001) 1255]. We found that Xrs2p, but not Mre11p or Rad50p, is efficiently phosphorylated in vitro by immunopreciptated Tel1p. Strains with mutations eliminating all SQ and TQ motifs in Xrs2p (preferred targets of the ATM kinase family) had wild-type length telomeres and wild-type sensitivity to DNA damaging agents. We also showed that Rfa2p (a subunit of RPA) and the Dun1p checkpoint kinase, which are required for DNA damage repair and which are phosphorylated in response to DNA damage in vivo, are in vitro substrates of the Tel1p and Mec1p kinases. In addition, Dun1p substrates with no SQ or TQ motifs are phosphorylated by Mec1p in vitro very inefficiently, but retain most of their ability to be phosphorylated by Tel1p. We demonstrated that null alleles of DUN1 and certain mutant alleles of RFA2 result in short telomeres. As observed with Xrs2p, however, strains with mutations of DUN1 or RFA2 that eliminate SQ motifs have no effect on telomere length or DNA damage sensitivity.

journal_name

DNA Repair (Amst)

journal_title

DNA repair

authors

Mallory JC,Bashkirov VI,Trujillo KM,Solinger JA,Dominska M,Sung P,Heyer WD,Petes TD

doi

10.1016/s1568-7864(03)00115-0

keywords:

subject

Has Abstract

pub_date

2003-09-18 00:00:00

pages

1041-64

issue

9

eissn

1568-7864

issn

1568-7856

pii

S1568786403001150

journal_volume

2

pub_type

杂志文章
  • The role of ATM and ATR in the cellular response to hypoxia and re-oxygenation.

    abstract::ATM and ATR are stress-response kinases which respond to a variety of insults including ionizing radiation, replication arrest, ultraviolet radiation and hypoxia/re-oxygenation. Hypoxia occupies a unique niche in the study of both ATR- and ATM-mediated checkpoint pathways. Hypoxia is a physiologically significant stre...

    journal_title:DNA repair

    pub_type: 杂志文章,评审

    doi:10.1016/j.dnarep.2004.03.035

    authors: Hammond EM,Giaccia AJ

    更新日期:2004-08-01 00:00:00

  • Deciphering phenotypic variance in different models of DNA-PKcs deficiency.

    abstract::DNA-PKcs deficiency has been studied in numerous animal models and cell culture systems. In previous studies of kinase inactivating mutations in cell culture systems, ablation of DNA-PK's catalytic activity results in a cell phenotype that is virtually indistinguishable from that ascribed to complete loss of the enzym...

    journal_title:DNA repair

    pub_type: 杂志文章

    doi:10.1016/j.dnarep.2018.10.004

    authors: Neal JA,Meek K

    更新日期:2019-01-01 00:00:00

  • DNA polymerase I proofreading exonuclease activity is required for endonuclease V repair pathway both in vitro and in vivo.

    abstract::Deamination of adenine can occur spontaneously under physiological conditions to generate the highly mutagenic lesion, deoxyinosine (hypoxanthine deoxyribonucleotide, dI). In DNA, dI preferably pairs with cytosine rather than thymine and results in A:T to G:C transition mutations after DNA replication. The deamination...

    journal_title:DNA repair

    pub_type: 杂志文章

    doi:10.1016/j.dnarep.2018.02.005

    authors: Su KY,Lin LI,Goodman SD,Yen RS,Wu CY,Chang WC,Yang YC,Cheng WC,Fang WH

    更新日期:2018-04-01 00:00:00

  • SSB recruitment of Exonuclease I aborts template-switching in Escherichia coli.

    abstract::Misalignment of a nascent strand and the use of an alternative template during DNA replication, a process termed "template-switching", can give rise to frequent mutations and genetic rearrangements. Mutational hotspots are frequently found associated with imperfect inverted repeats ("quasipalindromes" or "QPs") in man...

    journal_title:DNA repair

    pub_type: 杂志文章

    doi:10.1016/j.dnarep.2017.05.007

    authors: Laranjo LT,Gross SJ,Zeiger DM,Lovett ST

    更新日期:2017-09-01 00:00:00

  • Recruitment to stalled replication forks of the PriA DNA helicase and replisome-loading activities is essential for survival.

    abstract::PriA, a 3'-->5' superfamily 2 DNA helicase, acts to remodel stalled replication forks and as a specificity factor for origin-independent assembly of a new replisome at the stalled fork. The ability of PriA to initiate replication at stalled forked structures ensures complete genome replication and helps to protect the...

    journal_title:DNA repair

    pub_type: 杂志文章,评审

    doi:10.1016/j.dnarep.2009.12.009

    authors: Gabbai CB,Marians KJ

    更新日期:2010-03-02 00:00:00

  • TP53 and lacZ mutagenesis induced by 3-nitrobenzanthrone in Xpa-deficient human TP53 knock-in mouse embryo fibroblasts.

    abstract::3-Nitrobenzanthrone (3-NBA) is a highly mutagenic compound and possible human carcinogen found in diesel exhaust. 3-NBA forms bulky DNA adducts following metabolic activation and induces predominantly G:CT:A transversions in a variety of experimental systems. Here we investigated the influence of nucleotide excision r...

    journal_title:DNA repair

    pub_type: 杂志文章

    doi:10.1016/j.dnarep.2015.11.004

    authors: Kucab JE,Zwart EP,van Steeg H,Luijten M,Schmeiser HH,Phillips DH,Arlt VM

    更新日期:2016-03-01 00:00:00

  • Exo1 independent DNA mismatch repair involves multiple compensatory nucleases.

    abstract::Functional DNA mismatch repair (MMR) is essential for maintaining the fidelity of DNA replication and genetic stability. In hematopoiesis, loss of MMR results in methylating agent resistance and a hematopoietic stem cell (HSC) repopulation defect. Additionally MMR failure is associated with a variety of human malignan...

    journal_title:DNA repair

    pub_type: 杂志文章

    doi:10.1016/j.dnarep.2014.06.005

    authors: Desai A,Gerson S

    更新日期:2014-09-01 00:00:00

  • Conserved helicase domain of human RecQ4 is required for strand annealing-independent DNA unwinding.

    abstract::Humans have five members of the well conserved RecQ helicase family: RecQ1, Bloom syndrome protein (BLM), Werner syndrome protein (WRN), RecQ4, and RecQ5, which are all known for their roles in maintaining genome stability. BLM, WRN, and RecQ4 are associated with premature aging and cancer predisposition. Of the three...

    journal_title:DNA repair

    pub_type: 杂志文章

    doi:10.1016/j.dnarep.2010.04.003

    authors: Rossi ML,Ghosh AK,Kulikowicz T,Croteau DL,Bohr VA

    更新日期:2010-07-01 00:00:00

  • APE1: A skilled nucleic acid surgeon.

    abstract::Before a deleterious DNA lesion can be replaced with its undamaged counterpart, the lesion must first be removed from the genome. This process of removing and replacing DNA lesions is accomplished by the careful coordination of several protein factors during DNA repair. One such factor is the multifunctional enzyme hu...

    journal_title:DNA repair

    pub_type: 杂志文章,评审

    doi:10.1016/j.dnarep.2018.08.012

    authors: Whitaker AM,Freudenthal BD

    更新日期:2018-11-01 00:00:00

  • Developmental retinal apoptosis in Ku86-/- mice.

    abstract::The nonhomologous DNA end-joining pathway (NHEJ), a major pathway for repairing DNA double-strand breaks (DSBs), is essential for maintaining genomic stability. Knockout animals for components in this pathway demonstrate a distinct pattern of cell death in the developing brain. Here we demonstrate that cell death is a...

    journal_title:DNA repair

    pub_type: 杂志文章

    doi:10.1016/j.dnarep.2003.08.011

    authors: Karanjawala ZE,Hinton DR,Oh E,Hsieh CL,Lieber MR

    更新日期:2003-12-09 00:00:00

  • Repair of the mutagenic DNA oxidation product, 5-formyluracil.

    abstract::The oxidation of the thymine methyl group can generate 5-formyluracil (FoU). Template FoU residues are known to miscode, generating base substitution mutations. The repair of the FoU lesion is therefore important in minimizing mutations induced by DNA oxidation. We have studied the repair of FoU in synthetic oligonucl...

    journal_title:DNA repair

    pub_type: 杂志文章

    doi:10.1016/s1568-7864(02)00198-2

    authors: Liu P,Burdzy A,Sowers LC

    更新日期:2003-02-03 00:00:00

  • Mutational analysis of Thermococcus kodakarensis Endonuclease III reveals the roles of evolutionarily conserved residues.

    abstract::Endonuclease III (EndoIII) is nearly ubiquitous in all three domains of life. EndoIII family proteins exhibit a bifunctional (glycosylase/lyase) activity on oxidative/saturated pyrimidine bases, such as thymine glycol. Previous studies on EndoIII homologs have reported the presence of important residues involved in su...

    journal_title:DNA repair

    pub_type: 杂志文章

    doi:10.1016/j.dnarep.2020.102859

    authors: Shiraishi M,Mizutani K,Yamamoto J,Iwai S

    更新日期:2020-06-01 00:00:00

  • A method to accurately quantitate intensities of (32)P-DNA bands when multiple bands appear in a single lane of a gel is used to study dNTP insertion opposite a benzo[a]pyrene-dG adduct by Sulfolobus DNA polymerases Dpo4 and Dbh.

    abstract::Quantitating relative (32)P-band intensity in gels is desired, e.g., to study primer-extension kinetics of DNA polymerases (DNAPs). Following imaging, multiple (32)P-bands are often present in lanes. Though individual bands appear by eye to be simple and well-resolved, scanning reveals they are actually skewed-Gaussia...

    journal_title:DNA repair

    pub_type: 杂志文章

    doi:10.1016/j.dnarep.2014.10.001

    authors: Sholder G,Loechler EL

    更新日期:2015-01-01 00:00:00

  • Endogenous levels of Rad51 and Brca2 are required for homologous recombination and regulated by homeostatic re-balancing.

    abstract::Stable expression of Rad51 siRNA was used to generate mouse hybridoma cell lines in which endogenous Rad51 levels were depleted by as much as 60%. Stable Rad51 knockdowns feature reduced homologous recombination responses. The relative ease with which stable Rad51 knockdowns were recovered was surprising, given the em...

    journal_title:DNA repair

    pub_type: 杂志文章

    doi:10.1016/j.dnarep.2013.10.006

    authors: Magwood AC,Malysewich MJ,Cealic I,Mundia MM,Knapp J,Baker MD

    更新日期:2013-12-01 00:00:00

  • Removal of deoxyinosine from the Escherichia coli chromosome as studied by oligonucleotide transformation.

    abstract::Deoxyinosine (dI) is produced in DNA by the hydrolytic or nitrosative deamination of deoxyadenosine. It is excised in a repair pathway that is initiated by endonuclease V, the product of the nfi gene. The repair was studied in vivo using high-efficiency oligonucleotide transformation mediated by the Beta protein of ba...

    journal_title:DNA repair

    pub_type: 杂志文章

    doi:10.1016/j.dnarep.2007.09.010

    authors: Weiss B

    更新日期:2008-02-01 00:00:00

  • Deficient global genome repair of UV-induced cyclobutane pyrimidine dimers in terminally differentiated myocytes and proliferating fibroblasts from the rat heart.

    abstract::Nucleotide excision repair (NER) is the principal pathway for the removal of a wide range of DNA helix-distorting lesions. Two NER subpathways have been identified, i.e. global genome repair (GGR) and transcription-coupled repair (TCR). Little is known about the expression of NER pathways in differentiated cells. We a...

    journal_title:DNA repair

    pub_type: 杂志文章

    doi:10.1016/j.dnarep.2003.06.001

    authors: van der Wees CG,Vreeswijk MP,Persoon M,van der Laarse A,van Zeeland AA,Mullenders LH

    更新日期:2003-12-09 00:00:00

  • Activation of cellular signaling by 8-oxoguanine DNA glycosylase-1-initiated DNA base excision repair.

    abstract::Accumulation of 8-oxo-7,8-dihydroguanine (8-oxoG) in the DNA results in genetic instability and mutagenesis, and is believed to contribute to carcinogenesis, aging processes and various aging-related diseases. 8-OxoG is removed from the DNA via DNA base excision repair (BER), initiated by 8-oxoguanine DNA glycosylase-...

    journal_title:DNA repair

    pub_type: 杂志文章

    doi:10.1016/j.dnarep.2013.06.006

    authors: German P,Szaniszlo P,Hajas G,Radak Z,Bacsi A,Hazra TK,Hegde ML,Ba X,Boldogh I

    更新日期:2013-10-01 00:00:00

  • Archaeal DNA uracil repair via direct strand incision: A minimal system reconstituted from purified components.

    abstract::Hydrolytic deamination of DNA cytosine residues results in U/G mispairs, pre-mutagenic lesions threatening long-term genetic stability. Hence, DNA uracil repair is ubiquitous throughout all extant life forms and base excision repair, triggered by a uracil DNA glycosylase (UDG), is the mechanistic paradigm adopted, as ...

    journal_title:DNA repair

    pub_type: 杂志文章

    doi:10.1016/j.dnarep.2010.01.004

    authors: Schomacher L,Schürer KA,Ciirdaeva E,McDermott P,Chong JP,Kramer W,Fritz HJ

    更新日期:2010-04-04 00:00:00

  • XPA protein as a limiting factor for nucleotide excision repair and UV sensitivity in human cells.

    abstract::Nucleotide excision repair (NER) acts on a variety of DNA lesions, including damage induced by many chemotherapeutic drugs. Cancer therapy with such drugs might be improved by reducing the NER capacity of tumors. It is not known, however to what extent any individual NER protein is rate-limiting for any step of the re...

    journal_title:DNA repair

    pub_type: 杂志文章

    doi:10.1016/j.dnarep.2005.12.001

    authors: Köberle B,Roginskaya V,Wood RD

    更新日期:2006-05-10 00:00:00

  • Poetry in motion: Increased chromosomal mobility after DNA damage.

    abstract::Double-strand breaks (DSBs) are among the most lethal DNA lesions, and a variety of pathways have evolved to manage their repair in a timely fashion. One such pathway is homologous recombination (HR), in which information from an undamaged donor site is used as a template for repair. Although many of the biochemical s...

    journal_title:DNA repair

    pub_type: 杂志文章,评审

    doi:10.1016/j.dnarep.2017.06.012

    authors: Smith MJ,Rothstein R

    更新日期:2017-08-01 00:00:00

  • Defect of Fe-S cluster binding by DNA polymerase δ in yeast suppresses UV-induced mutagenesis, but enhances DNA polymerase ζ - dependent spontaneous mutagenesis.

    abstract::Eukaryotic genomes are duplicated by a complex machinery, utilizing high fidelity replicative B-family DNA polymerases (pols) α, δ and ε. Specialized error-prone pol ζ, the fourth B-family member, is recruited when DNA synthesis by the accurate trio is impeded by replication stress or DNA damage. The damage tolerance ...

    journal_title:DNA repair

    pub_type: 杂志文章

    doi:10.1016/j.dnarep.2016.11.004

    authors: Stepchenkova EI,Tarakhovskaya ER,Siebler HM,Pavlov YI

    更新日期:2017-01-01 00:00:00

  • Defects in recombination activity caused by somatic and germline mutations in the multimerization/BRCA2 binding region of human RAD51 protein.

    abstract::The human RAD51 recombinase possesses DNA pairing and strand exchange activities that are essential for the error-free, homology-directed repair of DNA double-strand breaks. The recombination activities of RAD51 are activated upon its assembly into presynaptic filaments on single-stranded DNA at resected DSB ends. Def...

    journal_title:DNA repair

    pub_type: 杂志文章

    doi:10.1016/j.dnarep.2017.10.008

    authors: Silva MC,Bryan KE,Morrical MD,Averill AM,Dragon J,Wiegmans AP,Morrical SW

    更新日期:2017-12-01 00:00:00

  • Telomeres and chromosome instability.

    abstract::Genomic instability has been proposed to play an important role in cancer by accelerating the accumulation of genetic changes responsible for cancer cell evolution. One mechanism for chromosome instability is through the loss of telomeres, which are DNA-protein complexes that protect the ends of chromosomes and preven...

    journal_title:DNA repair

    pub_type: 杂志文章,评审

    doi:10.1016/j.dnarep.2006.05.030

    authors: Murnane JP

    更新日期:2006-09-08 00:00:00

  • Mice defective in the mismatch repair gene Msh2 show increased predisposition to UVB radiation-induced skin cancer.

    abstract::Mice defective in the mismatch repair (MMR) gene Msh2 manifest an enhanced predisposition to skin cancer associated with exposure to UVB radiation. This predisposition is further heightened if the mice are additionally defective for the nucleotide excision repair gene Xpc. To test the hypothesis that the predispositio...

    journal_title:DNA repair

    pub_type: 杂志文章

    doi:10.1016/s1568-7864(02)00143-x

    authors: Meira LB,Cheo DL,Reis AM,Claij N,Burns DK,te Riele H,Friedberg EC

    更新日期:2002-11-03 00:00:00

  • Msh1p counteracts oxidative lesion-induced instability of mtDNA and stimulates mitochondrial recombination in Saccharomyces cerevisiae.

    abstract::The proximity of the mitochondrial genome to the respiratory chain, a major source of ROS (radical oxygen species), makes mtDNA more vulnerable to oxidative damage than nuclear DNA. Mitochondrial BER (base excision repair) is generally considered to be the main pathway involved in the prevention of oxidative lesion-in...

    journal_title:DNA repair

    pub_type: 杂志文章

    doi:10.1016/j.dnarep.2008.11.004

    authors: Kaniak A,Dzierzbicki P,Rogowska AT,Malc E,Fikus M,Ciesla Z

    更新日期:2009-03-01 00:00:00

  • Molecular basis for the functions of a bacterial MutS2 in DNA repair and recombination.

    abstract::Bacterial MutS2 proteins, consisting of functional domains for ATPase, DNA-binding, and nuclease activities, play roles in DNA recombination and repair. Here we observe a mechanism for generating MutS2 expression diversity in the human pathogen Helicobacter pylori, and identify a unique MutS2 domain responsible for sp...

    journal_title:DNA repair

    pub_type: 杂志文章

    doi:10.1016/j.dnarep.2017.07.004

    authors: Wang G,Maier RJ

    更新日期:2017-09-01 00:00:00

  • Base excision repair and nucleotide excision repair contribute to the removal of N-methylpurines from active genes.

    abstract::Many different cellular pathways have evolved to protect the genome from the deleterious effects of DNA damage that result from exposure to chemical and physical agents. Among these is a process called transcription-coupled repair (TCR) that catalyzes the removal of DNA lesions from the transcribed strand of expressed...

    journal_title:DNA repair

    pub_type: 杂志文章

    doi:10.1016/s1568-7864(02)00075-7

    authors: Plosky B,Samson L,Engelward BP,Gold B,Schlaen B,Millas T,Magnotti M,Schor J,Scicchitano DA

    更新日期:2002-08-06 00:00:00

  • Is RecG a general guardian of the bacterial genome?

    abstract::The RecG protein of Escherichia coli is a double-stranded DNA translocase that unwinds a variety of branched DNAs in vitro, including Holliday junctions, replication forks, D-loops and R-loops. Coupled with the reported pleiotropy of recG mutations, this broad range of potential targets has made it hard to pin down wh...

    journal_title:DNA repair

    pub_type: 杂志文章,评审

    doi:10.1016/j.dnarep.2009.12.014

    authors: Rudolph CJ,Upton AL,Briggs GS,Lloyd RG

    更新日期:2010-03-02 00:00:00

  • DNA mismatch repair mediates protection from mutagenesis induced by short-wave ultraviolet light.

    abstract::To investigate involvement of DNA mismatch repair in the response to short-wave ultraviolet (UVC) light, we compared UVC-induced mutant frequencies and mutational spectra at the Hprt gene between wild type and mismatch-repair-deficient mouse embryonic stem (ES) cells. Whereas mismatch repair gene status did not signif...

    journal_title:DNA repair

    pub_type: 杂志文章

    doi:10.1016/j.dnarep.2006.06.005

    authors: Borgdorff V,Pauw B,van Hees-Stuivenberg S,de Wind N

    更新日期:2006-11-08 00:00:00

  • Replication stalling and heteroduplex formation within CAG/CTG trinucleotide repeats by mismatch repair.

    abstract::Trinucleotide repeat expansions are responsible for at least two dozen neurological disorders. Mechanisms leading to these large expansions of repeated DNA are still poorly understood. It was proposed that transient stalling of the replication fork by the repeat tract might trigger slippage of the newly-synthesized st...

    journal_title:DNA repair

    pub_type: 杂志文章

    doi:10.1016/j.dnarep.2016.03.002

    authors: Viterbo D,Michoud G,Mosbach V,Dujon B,Richard GF

    更新日期:2016-06-01 00:00:00