Meiotic recombination and segregation of human-derived artificial chromosomes in Saccharomyces cerevisiae

D. D. Sears, J. H. Hegemann, P. Hieter

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

We have developed a system that utilizes human DNA-derived yeast artificial chromosomes (YACs) as marker chromosomes to study factors that contribute to the fidelity of meiotic chromosome transmission. Since aneuploidy for the YACs does not affect spore viability, different classes of meiotic missegregation can be scored accurately in four-viable-spore tetrads including precocious sister separation, meiosis I nondisjunction, meiotic chromatid loss, and meiosis II nondisjunction. Segregation of the homologous pair of 360-kilobase marker YACs was shown to occur with high fidelity in the first meiotic division and was associated with a high frequency of recombination within the human DNA segment. By using this experimental system, a series of YAC deletion derivatives ranging in size from 50 to 225 kilobases was analyzed to directly assess the relationship between meiotic recombination and meiosis I disjunction in a genotypically wild-type background. The relationship between physical distance and recombination frequency within the human DNA segment was measured to be comparable to that of endogenous yeast chromosomal DNA-ranging from <2.0 to 7.7 kilobases/centimorgan. Physical analysis of recombinant chromosomes detected no unequal crossing-over at dispersed repetitive elements distributed along the YACs. Recombination between YACs containing unrelated DNA segments was not observed. Furthermore, the segregational data indicated that meioses in which YAC pairs failed to recombine exhibited dramatically increased levels of meiosis I missegregation, including both precocious sister chromatid separation and nondisjunction.

Original languageEnglish (US)
Pages (from-to)5296-5300
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number12
DOIs
StatePublished - 1992

Keywords

  • chromosome segregation
  • meiosis
  • recombination
  • yeast artificial chromosomes

ASJC Scopus subject areas

  • General

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