The Saccharomyces cerevisiae Ku autoantigen homologue affects radiosensitivity only in the absence of homologous recombination

Wolfram Siede, Anna A. Friedl, Irina Dianova, Friederike Eckardt-Schupp, Errol C. Friedberg

Research output: Contribution to journalArticle

162 Citations (Scopus)

Abstract

In mammalian cells, all subunits of the DNA-dependent protein kinase (DNA- PK) have been implicated in the repair of DNA double-strand breaks and in V(D)J recombination. In the yeast, Saccharomyces cerevisiae, we have examined the phenotype conferred by a deletion of HDFI, the putative homologue of the 70-kD subunit of the DNA-end binding Ku complex of DNA-PK. The yeast gene does not play a role in radiation-induced cell cycle checkpoint arrest in G1 and G2 or in hydroxyurea-induced checkpoint arrest in S. In cells competent for homologous recombination, we could not detect any sensitivity to ionizing radiation or to methyl methanesulfonate (MMS) conferred by a hdfl deletion and indeed, the repair of DNA double-strand breaks was not impaired. However, if homologous recombination was disabled (rad52 mutant background), inactivation of HDFI results in additional sensitization toward ionizing radiation and MMS. These results give further support to the notion that, in contrast to higher eukaryotic cells, homologous recombination is the favored pathway of double-strand break repair in yeast whereas other competing mechanisms such as the suggested pathway of DNA-PK-dependent direct break rejoining are only of minor importance.

Original languageEnglish (US)
Pages (from-to)91-102
Number of pages12
JournalGenetics
Volume142
Issue number1
StatePublished - Jan 1996

Fingerprint

Radiation Tolerance
Homologous Recombination
Methyl Methanesulfonate
Saccharomyces cerevisiae
Double-Stranded DNA Breaks
Yeasts
Cell Cycle Checkpoints
Ionizing Radiation
DNA
DNA-Activated Protein Kinase
V(D)J Recombination
Hydroxyurea
Eukaryotic Cells
Radiation
Phenotype
Genes
Ku Autoantigen

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

The Saccharomyces cerevisiae Ku autoantigen homologue affects radiosensitivity only in the absence of homologous recombination. / Siede, Wolfram; Friedl, Anna A.; Dianova, Irina; Eckardt-Schupp, Friederike; Friedberg, Errol C.

In: Genetics, Vol. 142, No. 1, 01.1996, p. 91-102.

Research output: Contribution to journalArticle

Siede, Wolfram ; Friedl, Anna A. ; Dianova, Irina ; Eckardt-Schupp, Friederike ; Friedberg, Errol C. / The Saccharomyces cerevisiae Ku autoantigen homologue affects radiosensitivity only in the absence of homologous recombination. In: Genetics. 1996 ; Vol. 142, No. 1. pp. 91-102.
@article{e7b2094b2a1f4681b143547ed5d504fe,
title = "The Saccharomyces cerevisiae Ku autoantigen homologue affects radiosensitivity only in the absence of homologous recombination",
abstract = "In mammalian cells, all subunits of the DNA-dependent protein kinase (DNA- PK) have been implicated in the repair of DNA double-strand breaks and in V(D)J recombination. In the yeast, Saccharomyces cerevisiae, we have examined the phenotype conferred by a deletion of HDFI, the putative homologue of the 70-kD subunit of the DNA-end binding Ku complex of DNA-PK. The yeast gene does not play a role in radiation-induced cell cycle checkpoint arrest in G1 and G2 or in hydroxyurea-induced checkpoint arrest in S. In cells competent for homologous recombination, we could not detect any sensitivity to ionizing radiation or to methyl methanesulfonate (MMS) conferred by a hdfl deletion and indeed, the repair of DNA double-strand breaks was not impaired. However, if homologous recombination was disabled (rad52 mutant background), inactivation of HDFI results in additional sensitization toward ionizing radiation and MMS. These results give further support to the notion that, in contrast to higher eukaryotic cells, homologous recombination is the favored pathway of double-strand break repair in yeast whereas other competing mechanisms such as the suggested pathway of DNA-PK-dependent direct break rejoining are only of minor importance.",
author = "Wolfram Siede and Friedl, {Anna A.} and Irina Dianova and Friederike Eckardt-Schupp and Friedberg, {Errol C.}",
year = "1996",
month = "1",
language = "English (US)",
volume = "142",
pages = "91--102",
journal = "Genetics",
issn = "0016-6731",
publisher = "Genetics Society of America",
number = "1",

}

TY - JOUR

T1 - The Saccharomyces cerevisiae Ku autoantigen homologue affects radiosensitivity only in the absence of homologous recombination

AU - Siede, Wolfram

AU - Friedl, Anna A.

AU - Dianova, Irina

AU - Eckardt-Schupp, Friederike

AU - Friedberg, Errol C.

PY - 1996/1

Y1 - 1996/1

N2 - In mammalian cells, all subunits of the DNA-dependent protein kinase (DNA- PK) have been implicated in the repair of DNA double-strand breaks and in V(D)J recombination. In the yeast, Saccharomyces cerevisiae, we have examined the phenotype conferred by a deletion of HDFI, the putative homologue of the 70-kD subunit of the DNA-end binding Ku complex of DNA-PK. The yeast gene does not play a role in radiation-induced cell cycle checkpoint arrest in G1 and G2 or in hydroxyurea-induced checkpoint arrest in S. In cells competent for homologous recombination, we could not detect any sensitivity to ionizing radiation or to methyl methanesulfonate (MMS) conferred by a hdfl deletion and indeed, the repair of DNA double-strand breaks was not impaired. However, if homologous recombination was disabled (rad52 mutant background), inactivation of HDFI results in additional sensitization toward ionizing radiation and MMS. These results give further support to the notion that, in contrast to higher eukaryotic cells, homologous recombination is the favored pathway of double-strand break repair in yeast whereas other competing mechanisms such as the suggested pathway of DNA-PK-dependent direct break rejoining are only of minor importance.

AB - In mammalian cells, all subunits of the DNA-dependent protein kinase (DNA- PK) have been implicated in the repair of DNA double-strand breaks and in V(D)J recombination. In the yeast, Saccharomyces cerevisiae, we have examined the phenotype conferred by a deletion of HDFI, the putative homologue of the 70-kD subunit of the DNA-end binding Ku complex of DNA-PK. The yeast gene does not play a role in radiation-induced cell cycle checkpoint arrest in G1 and G2 or in hydroxyurea-induced checkpoint arrest in S. In cells competent for homologous recombination, we could not detect any sensitivity to ionizing radiation or to methyl methanesulfonate (MMS) conferred by a hdfl deletion and indeed, the repair of DNA double-strand breaks was not impaired. However, if homologous recombination was disabled (rad52 mutant background), inactivation of HDFI results in additional sensitization toward ionizing radiation and MMS. These results give further support to the notion that, in contrast to higher eukaryotic cells, homologous recombination is the favored pathway of double-strand break repair in yeast whereas other competing mechanisms such as the suggested pathway of DNA-PK-dependent direct break rejoining are only of minor importance.

UR - http://www.scopus.com/inward/record.url?scp=0030033061&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030033061&partnerID=8YFLogxK

M3 - Article

VL - 142

SP - 91

EP - 102

JO - Genetics

JF - Genetics

SN - 0016-6731

IS - 1

ER -