Loss of heterozygosity and DNA damage repair in Saccharomyces cerevisiae

Yasukazu Daigaku, Kingo Endo, Eri Watanabe, Tetsuya Ono, Kazuo Yamamoto

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

Loss of heterozygosity (LOH) of tumor suppressor genes is a crucial step in the development of sporadic and hereditary cancer. Understanding how LOH events arise may provide an opportunity for the prevention or early intervention of cancer development. In an effort to investigate the source of LOH events, we constructed MATα can1Δ::LEU2 and MATa CAN1 haploid yeast strains and examined canavanine-resistance mutations in a MATa CAN1/MATα can1Δ::LEU2 heterozygote formed by mating UV-irradiated and nonirradiated haploids. An increase in LOH was observed when the irradiated CAN1 haploid was mated with nonirradiated can1Δ::LEU2, while reversed irradiation only marginally increased LOH. In the rad51Δ background, allelic crossover type LOH increased following UV irradiation but not gene conversion. In the rad52Δ background, neither type of LOH increased. The chromosome structure following LOH and the requirement for Rad51 and Rad52 proteins indicated the involvement of gene conversion, allelic crossover and break-induced replication. We argued that LOH events could have occurred during the repair of double-strand breaks on a functional (damaged) but not nonfunctional (undamaged) chromosome through recombination.

Original languageEnglish
Pages (from-to)183-191
Number of pages9
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume556
Issue number1-2
DOIs
Publication statusPublished - 2004 Nov 22

Keywords

  • Break-induced replication
  • Canavanine-resistance
  • Gene conversion
  • Loss of heterozygosity
  • Saccharomyces cerevisiae

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis

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