文章基本信息

标题：Rad6-Bre1-mediated histone H2B ubiquitylation modulates the formation of double-strand breaks during meiosis
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作者：Kentaro Yamashita ; Miki Shinohara ; Akira Shinohara 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：31
页码：11380-11385
DOI：10.1073/pnas.0400078101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：An E2 ubiquitin-conjugating enzyme, Rad6, working with an E3 ubiquitin ligase Bre1, catalyzes monoubiquitylation of histone H2B on a C-terminal lysine residue. The rad6 mutant of Saccharomyces cerevisiae shows a meiotic prophase arrest. Here, we analyzed meiotic defects of a rad6 null mutant of budding yeast. The rad6 mutant exhibits pleiotropic phenotypes during meiosis. RAD6 is required for efficient formation of double-strand breaks (DSBs) at meiotic recombination hotspots, which is catalyzed by Spo11. The mutation decreases overall frequencies of DSBs in a cell. The effect of the rad6 mutation is local along chromosomes; levels of DSBs at stronger hotspots are particularly reduced in the mutant. The absence of RAD6 has little effect on the formation of ectopic DSBs targeted by Spo11 fusion protein with a Gal4 DNA-binding domain. Furthermore, the disruption of the BRE1 as well as substitution of the ubiquitylation site of histone H2B also reduces some DSB formation similar to the rad6. These results suggest that Rad6-Bre1, through ubiquitylation of histone H2B, is necessary for efficient recruitment and/or stabilization of a DSB-forming machinery containing Spo11. Histone tail modifications might play a role in DSB formation during meiosis.