Mieczkowski Piotr A, Dominska Margaret, Buck Michael J, Lieb Jason D, Petes Thomas D
Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA.
Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):3955-60. doi: 10.1073/pnas.0700412104. Epub 2007 Feb 28.
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.
在真核生物中，减数分裂重组事件在基因组中的分布并非随机，某些区域具有高水平的重组（热点），而其他区域则具有低水平的重组（冷点）。具有相似DNA序列的物种（例如黑猩猩和人类）可能具有截然不同的热点和冷点模式。下面，通过使用微阵列分析，使我们能够测量所有6000个酵母基因减数分裂特异性双链DNA断裂（DSB）的频率，我们发现编码组蛋白脱乙酰基酶的单个基因（SIR2）的突变显著改变了12%的酵母基因的DSB频率，使5%的基因的DSB增加，7%的基因的DSB减少。许多重组受到抑制的基因位于靠近端粒但不在端粒处的大（50-100 kb）区域。一些DSB频率发生改变的基因（包括核糖体RNA基因簇）是野生型菌株中Sir2p去乙酰化的已知靶点。
