Catalysis-dependent and redundant roles of Dma1 and Dma2 in maintenance of genome stability in Saccharomyces cerevisiae.
Catalysis-dependent and redundant roles of Dma1 and Dma2 in maintenance of genome stability in Saccharomyces cerevisiae.
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DOI：
10.1016/j.jbc.2021.100721
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Dronamraju R
中科院分区：
文献类型：
--
作者：
Yoblinski AR;Chung S;Robinson SB;Forester KE;Strahl BD;Dronamraju R
DNA双链断裂（DSBs）是一种内源性和外源性的有害损伤，通过非同源端连接或同源重组来修复。然而，维持基因组稳定性的分子机制仍然不完全清楚。在这里，我们研究了两个E3连接酶Dma1和Dma2（人类RNF8的同源物）在维持芽殖酵母基因组稳定性中的作用。通过酵母斑点测定、染色质免疫沉淀、质粒和染色体修复测定，我们确定Dma1和Dma2在维持基因组稳定性方面以冗余和催化依赖的方式起作用，并定位于基因组的转录区域，并在霉素治疗后丰度增加。此外，Dma1和Dma2是DNA损伤条件下组蛋白H4乙酰化的正常动力学所必需的，与RAD9和SAE2基因相互作用，并与Rad53和组蛋白形成复合物。总之，我们的研究结果证明了Dma1和Dma2在调节DNA修复途径选择方面的必要性，优先影响同源重组而不是非同源末端连接，并开辟了使用这些候选基因来操纵修复途径以实现精确基因组编辑的可能性。
DNA double-strand breaks (DSBs) are among the deleterious lesions that are both endogenous and exogenous in origin and are repaired by nonhomologous end joining or homologous recombination. However, the molecular mechanisms responsible for maintaining genome stability remain incompletely understood. Here, we investigate the role of two E3 ligases, Dma1 and Dma2 (homologs of human RNF8), in the maintenance of genome stability in budding yeast. Using yeast spotting assays, chromatin immunoprecipitation and plasmid and chromosomal repair assays, we establish that Dma1 and Dma2 act in a redundant and a catalysis-dependent manner in the maintenance of genome stability, as well as localize to transcribed regions of the genome and increase in abundance upon phleomycin treatment. In addition, Dma1 and Dma2 are required for the normal kinetics of histone H4 acetylation under DNA damage conditions, genetically interact with RAD9 and SAE2, and are in a complex with Rad53 and histones. Taken together, our results demonstrate the requirement of Dma1 and Dma2 in regulating DNA repair pathway choice, preferentially affecting homologous recombination over nonhomologous end joining, and open up the possibility of using these candidates in manipulating the repair pathways toward precision genome editing.
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DOI：
10.1042/bj20121425
发表时间：
2013-12-01
期刊：
The Biochemical journal
影响因子：
--
作者：
D'Cruz AA;Kershaw NJ;Chiang JJ;Wang MK;Nicola NA;Babon JJ;Gack MU;Nicholson SE
通讯作者：
Nicholson SE
影响因子：
3.4
作者：
Sardiello M;Cairo S;Fontanella B;Ballabio A;Meroni G
通讯作者：
Meroni G
DOI：
10.1038/nri2413
发表时间：
2008-11
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Ozato K;Shin DM;Chang TH;Morse HC 3rd
通讯作者：
Morse HC 3rd
影响因子：
4.8
作者：
Skurat, AV;Dietrich, AD;Roach, PJ
通讯作者：
Roach, PJ
影响因子：
16
作者：
Kato K;Ahmad S;Zhu Z;Young JM;Mu X;Park S;Malik HS;Hur S
通讯作者：
Hur S