Complementation between N-terminal Saccharomyces cerevisiae mre11 alleles in DNA repair and telomere length maintenance

Sang Lee, Debra A. Bressan, John H J Petrini, James E. Haber

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

In Saccharomyces cerevisiae, Mre11p, Rad50p, and Xrs2p function as a multiprotein complex that has a central role in several DNA repair mechanisms. Though Mre11p has both single-stranded and double-stranded 3′-5′ exonuclease activity in vitro, null mutants of MRE11, RAD50, and XRS2 exhibit reduced 5′-3′ resection of HO-induced double-strand breaks (DSBs) in vivo. In this study, we analyzed four mre11 mutants harboring changes in the N-terminus of Mre11p where the four phosphoesterase motifs specify the in vitro nuclease activities of Mre11p and its homologues. We find that the 5′-3′ resection defects in vivo do not correlate with several mitotic phenotypes: non-homologous end-joining (NHEJ), telomere length maintenance, and adaptation to the DNA damage-inducible G2/M checkpoint. Overexpression of the 5′-3′ exonuclease Exo1p in a mre11Δ strain partially increased 5′-3′ resection and partially suppressed both methyl methanesulfonate (MMS) hypersensitivity and adaptation phenotypes, but did not affect telomere length or NHEJ. Surprisingly, the co-expression of two alleles, mre11-58S and mre11-N113S, each of which confers MMS hypersensitivity and short telomeres, can fully complement the MMS sensitivity and shortened telomere length of mre11Δ cells. We propose that at least two separate activities associated with the N-terminus of Mre11p are required for its mitotic function.

Original languageEnglish (US)
Pages (from-to)27-40
Number of pages14
JournalDNA Repair
Volume1
Issue number1
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Telomere Homeostasis
Methyl Methanesulfonate
DNA Repair
Yeast
Saccharomyces cerevisiae
Exonucleases
Repair
Alleles
Telomere
Joining
DNA
Hypersensitivity
Telomere Shortening
Phenotype
Multiprotein Complexes
DNA Damage
Defects
In Vitro Techniques

Keywords

  • Cell cycle checkpoint
  • Double-strand break repair
  • MRE11
  • Saccharomyces cerevisiae
  • Telomere

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Complementation between N-terminal Saccharomyces cerevisiae mre11 alleles in DNA repair and telomere length maintenance. / Lee, Sang; Bressan, Debra A.; Petrini, John H J; Haber, James E.

In: DNA Repair, Vol. 1, No. 1, 2002, p. 27-40.

Research output: Contribution to journalArticle

Lee, Sang ; Bressan, Debra A. ; Petrini, John H J ; Haber, James E. / Complementation between N-terminal Saccharomyces cerevisiae mre11 alleles in DNA repair and telomere length maintenance. In: DNA Repair. 2002 ; Vol. 1, No. 1. pp. 27-40.
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