Chl1p, a DNA helicase-like protein in budding yeast, functions in sister-chromatid cohesion

Genetics. 2004 Jan;166(1):33-42. doi: 10.1534/genetics.166.1.33.

Abstract

From the time of DNA replication until anaphase onset, sister chromatids remain tightly paired along their length. Ctf7p/Eco1p is essential to establish sister-chromatid pairing during S-phase and associates with DNA replication components. DNA helicases precede the DNA replication fork and thus will first encounter chromatin sites destined for cohesion. In this study, I provide the first evidence that a DNA helicase is required for proper sister-chromatid cohesion. Characterizations of chl1 mutant cells reveal that CHL1 interacts genetically with both CTF7/ECO1 and CTF18/CHL12, two genes that function in sister-chromatid cohesion. Consistent with genetic interactions, Chl1p physically associates with Ctf7p/Eco1p both in vivo and in vitro. Finally, a functional assay reveals that Chl1p is critical for sister-chromatid cohesion. Within the budding yeast genome, Chl1p exhibits the highest degree of sequence similarity to human CHL1 isoforms and BACH1. Previous studies revealed that human CHLR1 exhibits DNA helicase-like activities and that BACH1 is a helicase-like protein that associates with the tumor suppressor BRCA1 to maintain genome integrity. Our findings document a novel role for Chl1p in sister-chromatid cohesion and provide new insights into the possible mechanisms through which DNA helicases may contribute to cancer progression when mutated.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetyltransferases*
  • Amino Acid Sequence
  • Base Sequence
  • Basic-Leucine Zipper Transcription Factors
  • Chromatids / genetics
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosomal Proteins, Non-Histone / metabolism
  • DNA Helicases / genetics*
  • DNA Helicases / metabolism
  • DNA, Fungal / genetics
  • Fanconi Anemia Complementation Group Proteins
  • Genes, Fungal
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Transcription Factors / genetics

Substances

  • BACH1 protein, human
  • Basic-Leucine Zipper Transcription Factors
  • CHL1 protein, S cerevisiae
  • CTF18 protein, S cerevisiae
  • Chromosomal Proteins, Non-Histone
  • DNA, Fungal
  • Fanconi Anemia Complementation Group Proteins
  • Nuclear Proteins
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Acetyltransferases
  • ECO1 protein, S cerevisiae
  • DNA Helicases