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Molecular and Cellular Biology, May 2000, p. 3449-3458, Vol. 20, No. 10
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Long Palindromic Sequences Induce Double-Strand
Breaks during Meiosis in Yeast
Farooq
Nasar,1
Craig
Jankowski,1 and
Dilip K.
Nag1,2,*
Molecular Genetics Program, Wadsworth
Center,1 and Department of Biomedical
Sciences, School of Public Health, State University of New
York,2 Albany, New York 12201
Received 9 December 1999/Returned for modification 7 February
2000/Accepted 28 February 2000
Inverted-repeated or palindromic sequences have been found to occur
in both prokaryotic and eukaryotic genomes. Such repeated sequences are
usually short and present at several functionally important regions in
the genome. However, long palindromic sequences are rare and are a
major source of genomic instability. The palindrome-mediated genomic
instability is believed to be due to cruciform or hairpin formation and
subsequent cleavage of this structure by structure-specific nucleases.
Here we present both genetic and physical evidence that long
palindromic sequences (>50 bp) generate double-strand breaks (DSBs) at
a high frequency during meiosis in the yeast Saccharomyces
cerevisiae. The palindrome-mediated DSB formation depends on the
primary sequence of the inverted repeat and the location and length of
the repeated units. The DSB formation at the palindrome requires all of
the gene products that are known to be responsible for DSB formation at
the normal meiosis-specific sites. Since DSBs are initiators of nearly
all meiotic recombination events, most of the palindrome-induced breaks
appear to be repaired by homologous recombination. Our results suggest
that short palindromic sequences are highly stable in vivo. In
contrast, long palindromic sequences make the genome unstable by
inducing DSBs and such sequences are usually removed from the genome by
homologous recombination events.
*
Corresponding author. Mailing address: Molecular
Genetics Program, Wadsworth Center, 120 New Scotland Ave., Albany, NY
12201-2002. Phone: (518) 473-6327. Fax: (518) 474-3181. E-mail:
dilip.nag{at}wadsworth.org.
Molecular and Cellular Biology, May 2000, p. 3449-3458, Vol. 20, No. 10
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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