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Molecular and Cellular Biology, February 2002, p. 953-964, Vol. 22, No. 3
0270-7306/01/$04.00+0     DOI: 10.1128/MCB.22.3.953-964.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

RAD1 Controls the Meiotic Expansion of the Human HRAS1 Minisatellite in Saccharomyces cerevisiae

Peter A. Jauert,1 Sharon N. Edmiston,2 Kathleen Conway,2 and David T. Kirkpatrick1*

Department of Genetics, Cell Biology, and Development, University of Minnesota, Saint Paul, Minnesota 55108,1 Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-74002

Received 11 July 2001/ Returned for modification 13 August 2001/ Accepted 6 November 2001

Minisatellite DNA is repetitive DNA with a repeat unit length from 15 to 100 bp. While stable during mitosis, it destabilizes during meiosis, altering both in length and in sequence composition. The basis for this instability is unknown. To investigate the factors controlling minisatellite stability, a minisatellite sequence 3' of the human HRAS1 gene was introduced into the Saccharomyces cerevisiae genome, replacing the wild-type HIS4 promoter. The minisatellite tract exhibited the same phenotypes in yeast that it exhibited in mammalian systems. The insertion stimulated transcription of the HIS4 gene; mRNA production was detected at levels above those seen with the wild-type promoter. The insertion stimulated meiotic recombination and created a hot spot for initiation of double-strand breaks during meiosis in the regions immediately flanking the repetitive DNA. The tract length altered at a high frequency during meiosis, and both expansions and contractions in length were detected. Tract expansion, but not contraction, was controlled by the product of the RAD1 gene. RAD1 is the first gene identified that controls specifically the expansion of minisatellite tracts. A model for tract length alteration based on these results is presented.

* Corresponding author. Mailing address: Department of Genetics, Cell Biology and Development, University of Minnesota, 250 Biological Sciences, 1445 Gortner Ave., Saint Paul, MN 55108. Phone: (612) 624-9244. Fax: (612) 625-5754. E-mail: dkirkpat{at}biosci.cbs.umn.edu.

Molecular and Cellular Biology, February 2002, p. 953-964, Vol. 22, No. 3
0022-538X/01/$04.00+0     DOI: 10.1128/MCB.22.3.953-964.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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