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Abstract

In eukaryotes a cell-cycle control termed a checkpoint causes arrest in the S or G2 phases when chromosomes are incompletely replicated or damaged. Previously, we showed in budding yeast that RAD9 and RAD17 are checkpoint genes required for arrest in the G2 phase after DNA damage. Here, we describe a genetic strategy that identified four additional checkpoint genes that act in two pathways. Both classes of genes are required for arrest in the G2 phase after DNA damage, and one class of genes is also required for arrest in S phase when DNA replication is incomplete. The G2-specific genes include MEC3 (for mitosis entry checkpoint), RAD9, RAD17, and RAD24. The genes common to both S phase and G2 phase pathways are MEC1 and MEC2. The MEC2 gene proves to be identical to the RAD53 gene. Checkpoint mutants were identified by their interactions with a temperature-sensitive allele of the cell division cycle gene CDC13; cdc13 mutants arrested in G2 and survived at the restrictive temperature, whereas all cdc13 checkpoint double mutants failed to arrest in G2 and died rapidly at the restrictive temperature. The cell-cycle roles of the RAD and MEC genes were examined by combination of rad and mec mutant alleles with 10 cdc mutant alleles that arrest in different stages of the cell cycle at the restrictive temperature and by the response of rad and mec mutant alleles to DNA damaging agents and to hydroxyurea, a drug that inhibits DNA replication. We conclude that the checkpoint in budding yeast consists of overlapping S-phase and G2-phase pathways that respond to incomplete DNA replication and/or DNA damage and cause arrest of cells before mitosis.

Original languageEnglish (US)
Pages (from-to)652-665
Number of pages14
JournalGenes and Development
Volume8
Issue number6
StatePublished - Mar 15 1994

Fingerprint

M Phase Cell Cycle Checkpoints
Saccharomycetales
DNA Replication
Mitosis
DNA Repair
G2 Phase
Genes
S Phase
Alleles
DNA Damage
Temperature
Cell Cycle
cdc Genes
Hydroxyurea
Cell Cycle Checkpoints
Eukaryota
Chromosomes

Keywords

  • budding yeast
  • cell-cycle control
  • Checkpoints
  • DNA replication and repair

ASJC Scopus subject areas

  • Developmental Biology
  • Genetics

Cite this

Mitotic checkpoint genes in budding yeast and the dependence of mitosis on DNA replication and repair. / Weinert, Ted A.; Kiser, Gretchen L.; Hartwell, Leland.

In: Genes and Development, Vol. 8, No. 6, 15.03.1994, p. 652-665.

Research output: Contribution to journalArticle

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