Factors That Affect the Location and Frequency of Meiosis-Induced Double-Strand Breaks in Saccharomyces cerevisiae

INVESTIGATIONS

Factors That Affect the Location and Frequency of Meiosis-Induced Double-Strand Breaks in Saccharomyces cerevisiae

T. C. Wu and M. Lichten
Laboratory of Biochemistry, Division of Cancer Biology, Diagnosis and Centers, National Cancer Institute, Bethesda, Maryland 20892

Double-strand DNA breaks (DSBs) initiate meiotic recombination in Saccharomyces cerevisiae. DSBs occur at sites that are hypersensitive in nuclease digests of chromatin, suggesting a role for chromatin structure in determining DSB location. We show here that the frequency of DSBs at a site is not determined simply by DNA sequence or by features of chromatin structure. An arg4-containing plasmid was inserted at several different locations in the yeast genome. Meiosis-induced DSBs occurred at similar sites in pBR322-derived portions of the construct at all insert loci, and the frequency of these breaks varied in a manner that mirrored the frequency of meiotic recombination in the arg4 portion of the insert. However, DSBs did not occur in the insert-borne arg4 gene at a site that is frequently broken at the normal ARG4 locus, even though the insert-borne arg4 gene and the normal ARG4 locus displayed similar DNase I hypersensitivity patterns. Deletions that removed active DSB sites from an insert at HIS4 restored breaks to the insert-borne arg4 gene and to a DSB site in flanking chromosomal sequences. We conclude that the frequency of DSB at a site can be affected by sequences several thousands nucleotides away and suggest that this is because of competition between DSB sites for locally limited factors.

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				L. Jessop, T. Allers, and M. Lichten Infrequent Co-conversion of Markers Flanking a Meiotic Recombination Initiation Site in Saccharomyces cerevisiae Genetics, March 1, 2005; 169(3): 1353 - 1367. [Abstract] [Full Text] [PDF]

				H. B. Schlecht, M. Lichten, and A. S. H. Goldman Compartmentalization of the Yeast Meiotic Nucleus Revealed by Analysis of Ectopic Recombination Genetics, November 1, 2004; 168(3): 1189 - 1203. [Abstract] [Full Text] [PDF]

				P. Houston, P. J. Simon, and J. R. Broach The Saccharomyces cerevisiae Recombination Enhancer Biases Recombination During Interchromosomal Mating-Type Switching but Not in Interchromosomal Homologous Recombination Genetics, March 1, 2004; 166(3): 1187 - 1197. [Abstract] [Full Text] [PDF]

				S. J. Haring, G. R. Halley, A. J. Jones, and R. E. Malone Properties of Natural Double-Strand-Break Sites at a Recombination Hotspot in Saccharomyces cerevisiae Genetics, September 1, 2003; 165(1): 101 - 114. [Abstract] [Full Text] [PDF]

				T. Schwarzacher Meiosis, recombination and chromosomes: a review of gene isolation and fluorescent in situ hybridization data in plants J. Exp. Bot., January 1, 2003; 54(380): 11 - 23. [Abstract] [Full Text] [PDF]

				T. D. Petes and J. D. Merker Context Dependence of Meiotic Recombination Hotspots in Yeast: The Relationship Between Recombination Activity of a Reporter Construct and Base Composition Genetics, December 1, 2002; 162(4): 2049 - 2052. [Abstract] [Full Text] [PDF]

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				M. F. F. Abdullah and R. H. Borts Meiotic recombination frequencies are affected by nutritional states in Saccharomycescerevisiae PNAS, November 20, 2001; (2001) 201529598. [Abstract] [Full Text] [PDF]

				H. M. Kearney, D. T. Kirkpatrick, J. L. Gerton, and T. D. Petes Meiotic Recombination Involving Heterozygous Large Insertions in Saccharomyces cerevisiae: Formation and Repair of Large, Unpaired DNA Loops Genetics, August 1, 2001; 158(4): 1457 - 1476. [Abstract] [Full Text] [PDF]

				S. M. Fullerton, A. Bernardo Carvalho, and A. G. Clark Local Rates of Recombination Are Positively Correlated with GC Content in the Human Genome Mol. Biol. Evol., June 1, 2001; 18(6): 1139 - 1142. [Full Text]

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				E. S. Davis, B. K. Shafer, and J. N. Strathern The Saccharomyces cerevisiae RDN1 Locus Is Sequestered From Interchromosomal Meiotic Ectopic Recombination in a SIR2-Dependent Manner Genetics, July 1, 2000; 155(3): 1019 - 1032. [Abstract] [Full Text]

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