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

Julia C. Mallory, Vladimir I. Bashkirov, Kelly M. Trujillo, Jachen A. Solinger, Margaret Dominska, Patrick Sung, Wolf Dietrich Heyer, Thomas D. Petes

Research output: Contribution to journalArticle

40 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1041-1064
Number of pages24
JournalDNA Repair
Volume2
Issue number9
DOIs
StatePublished - Sep 18 2003

Fingerprint

Ataxia Telangiectasia Mutated Proteins
Telomere
Automatic teller machines
DNA Repair
Yeast
Protein Kinases
DNA Damage
Saccharomyces cerevisiae
Repair
Amino Acids
Mutation
DNA
Phosphotransferases
Alleles
Genes
Saccharomyces
Eukaryota
DNA Replication
Gene encoding
Substrates

Keywords

  • ATM-related protein kinases
  • Checkpoints
  • Dun1p
  • Rfa2p
  • Telomeres
  • Xrs2p

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

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. / Mallory, Julia C.; Bashkirov, Vladimir I.; Trujillo, Kelly M.; Solinger, Jachen A.; Dominska, Margaret; Sung, Patrick; Heyer, Wolf Dietrich; Petes, Thomas D.

In: DNA Repair, Vol. 2, No. 9, 18.09.2003, p. 1041-1064.

Research output: Contribution to journalArticle

Mallory, Julia C. ; Bashkirov, Vladimir I. ; Trujillo, Kelly M. ; Solinger, Jachen A. ; Dominska, Margaret ; Sung, Patrick ; Heyer, Wolf Dietrich ; Petes, Thomas D. / 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. In: DNA Repair. 2003 ; Vol. 2, No. 9. pp. 1041-1064.
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T1 - 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

AU - Mallory, Julia C.

AU - Bashkirov, Vladimir I.

AU - Trujillo, Kelly M.

AU - Solinger, Jachen A.

AU - Dominska, Margaret

AU - Sung, Patrick

AU - Heyer, Wolf Dietrich

AU - Petes, Thomas D.

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