Loss of a histone deacetylase dramatically alters the genomic distribution of Spo11p-catalyzed DNA breaks in Saccharomyces cerevisiae.
In eukaryotes, meiotic recombination events are distributed nonrandomly in the genome, with certain regions having high levels of recombination (hotspots) and others having low levels (coldspots). Species with similar DNA sequences (for example, chimpanzees and humans) can have strikingly different patterns of hotspots and coldspots. Below, by using a microarray analysis that allows us to measure the frequency of the meiosis-specific double-strand DNA breaks (DSBs) of all 6,000 yeast genes, we show that mutation of a single gene (SIR2), which encodes a histone deacetylase, significantly changes DSB frequencies of 12% of yeast genes, elevating DSBs of 5%, and reducing DSBs of 7%. Many of the genes with repressed recombination are located in large (50-100 kb) regions located near, but not at, the telomeres. Some of the genes with altered frequencies of DSBs (including the ribosomal RNA gene cluster) are known targets of Sir2p deacetylation in the wild-type strain.
Mieczkowski
Piotr A
PA
Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA.
Dominska
Margaret
M
Buck
Michael J
MJ
Lieb
Jason D
JD
Petes
Thomas D
TD
D002384:Catalysis; D002843:Chromatin / Q000378:metabolism; D004249:DNA Damage; D004250:DNA Topoisomerases, Type II / Q000235:genetics* / Q000502:physiology*; D004271:DNA, Fungal; D004706:Endodeoxyribonucleases; D016678:Genome; D016681:Genome, Fungal; D006655:Histone Deacetylases / Q000378:metabolism / Q000502:physiology*; D008540:Meiosis; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D016366:Open Reading Frames; D011995:Recombination, Genetic; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D000099257:Meiotic Recombination Protein SPO11
D002843:Chromatin; D004250:DNA Topoisomerases, Type II; D004271:DNA, Fungal; D004706:Endodeoxyribonucleases; D006655:Histone Deacetylases; D029701:Saccharomyces cerevisiae Proteins; C518938:Spo11 protein, S cerevisiae; D000099257:Meiotic Recombination Protein SPO11