Reconstitution of a MEC1-independent checkpoint in yeast by expression of a novel human fork head cDNA

Debananda Pati, Charles Keller, Mark Groudine, Sharon E. Plon

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

A novel human cDNA, CHES1 (checkpoint suppressor l), has been isolated by suppression of the mecl-I checkpoint mutation in Saccharomyces cerevisiae. CHFS1 suppresses a number of DNA damage-activated checkpoint mutations in S. cerevisiae, including mec1, rad9, rad24, dun 1, and rad53. CHES I suppression of sensitivity to DNA damage is specific for checkpoint-defective strains, in contrast to DNA repair-defective strains. Presence of CHES1 but not a control vector resulted in G2 delay after UV irradiation in checkpoint-defective strains, with kinetics, nuclear morphology, and cycloheximide resistance similar to those of a wild-type strain. CHES1 can also suppress the lethality, UV sensitivity, and G2 checkpoint defect of a mec1 null mutation. In contrast to this activity, CHES1 had no measurable effect on the replication checkpoint as assayed by hydroxyurea sensitivity of a mec1 strain. Sequence analysis demonstrates that CHES1 is a novel member of the fork head/Winged Helix family of transcription factors. Suppression of the checkpoint-defective phenotype requires a 200-amino-acid domain in the carboxy terminus of the protein which is distinct from the DNA binding site. Analysis of CHESI activity is most consistent with activation of an alternative MEC1-independent checkpoint pathway in budding yeast.

Original languageEnglish (US)
Pages (from-to)3037-3046
Number of pages10
JournalMolecular and cellular biology
Volume17
Issue number6
DOIs
StatePublished - Jun 1997

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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