Skip to main content
Journal cover image

Dhh1 regulates the G1/S-checkpoint following DNA damage or BRCA1 expression in yeast.

Publication ,  Journal Article
Westmoreland, TJ; Olson, JA; Saito, WY; Huper, G; Marks, JR; Bennett, CB
Published in: J Surg Res
July 2003

BACKGROUND: Heterologous expression of the tumor suppressor BRCA1 in the yeast Saccharomyces cerevisiae is lethal. To identify potential new BRCA1-interacting gene targets, we characterized highly conserved ionizing radiation (IR) sensitive gene deletions that suppress BRCA1-induced lethality in yeast. MATERIALS AND METHODS: Previously, we exposed an isogenic collection of yeast strains individually deleted for 4746 nonessential genes to IR and identified 199 radiation sensitive deletion strains. A subset (n = 130) of these were screened for those that suppressed the G1 arrest and lethality observed following galactose-induced expression from a GAL::BRCA1 plasmid in wild type yeast. RESULTS: We found that deletions of two core components of the highly conserved CCR4-NOT transcription complex (CCR4 or DHH1) rescued BRCA1-induced G1 arrest and lethality in yeast. This was not because of down regulation of the GAL promoter since both deletion strains produce large amounts of BRCA1 that is rapidly degraded. In addition, heterologous expression of BRCA1 results in increased transcription of the DNA damage-inducible reporter construct DIN::LacZ. Reduced viability following IR and nitrogen starvation was observed among strains deleted for CCR4 or DHH1 because of a defect in G1 to S phase checkpoint transition. Lethality following nitrogen starvation and IR was partially rescued in dhh1Delta strains by expressing the human ortholog of DHH1 (DDX6) which has been identified as a breakpoint oncogene.T CONCLUSIONS: hese results suggest that BRCA1 may promote genomic stability in human cells by interacting with the highly conserved ortholog of DHH1 (DDX6) to properly activate G1/S checkpoint arrest following DNA damage.

Duke Scholars

Published In

J Surg Res

DOI

ISSN

0022-4804

Publication Date

July 2003

Volume

113

Issue

1

Start / End Page

62 / 73

Location

United States

Related Subject Headings

  • Transcription Factors
  • Surgery
  • Saccharomyces cerevisiae Proteins
  • Ribonucleases
  • RNA-Binding Proteins
  • RNA Helicases
  • Promoter Regions, Genetic
  • Nitrogen
  • Lac Operon
  • Interphase
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Westmoreland, T. J., Olson, J. A., Saito, W. Y., Huper, G., Marks, J. R., & Bennett, C. B. (2003). Dhh1 regulates the G1/S-checkpoint following DNA damage or BRCA1 expression in yeast. J Surg Res, 113(1), 62–73. https://doi.org/10.1016/s0022-4804(03)00155-0
Westmoreland, T. J., J. A. Olson, W. Y. Saito, G. Huper, J. R. Marks, and C. B. Bennett. “Dhh1 regulates the G1/S-checkpoint following DNA damage or BRCA1 expression in yeast.J Surg Res 113, no. 1 (July 2003): 62–73. https://doi.org/10.1016/s0022-4804(03)00155-0.
Westmoreland TJ, Olson JA, Saito WY, Huper G, Marks JR, Bennett CB. Dhh1 regulates the G1/S-checkpoint following DNA damage or BRCA1 expression in yeast. J Surg Res. 2003 Jul;113(1):62–73.
Westmoreland, T. J., et al. “Dhh1 regulates the G1/S-checkpoint following DNA damage or BRCA1 expression in yeast.J Surg Res, vol. 113, no. 1, July 2003, pp. 62–73. Pubmed, doi:10.1016/s0022-4804(03)00155-0.
Westmoreland TJ, Olson JA, Saito WY, Huper G, Marks JR, Bennett CB. Dhh1 regulates the G1/S-checkpoint following DNA damage or BRCA1 expression in yeast. J Surg Res. 2003 Jul;113(1):62–73.
Journal cover image

Published In

J Surg Res

DOI

ISSN

0022-4804

Publication Date

July 2003

Volume

113

Issue

1

Start / End Page

62 / 73

Location

United States

Related Subject Headings

  • Transcription Factors
  • Surgery
  • Saccharomyces cerevisiae Proteins
  • Ribonucleases
  • RNA-Binding Proteins
  • RNA Helicases
  • Promoter Regions, Genetic
  • Nitrogen
  • Lac Operon
  • Interphase