Stability across the Whole Nuclear Genome in the Presence and Absence of DNA Mismatch Repair.
Stability across the Whole Nuclear Genome in the Presence and Absence of DNA Mismatch Repair.
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DOI：
10.3390/cells10051224
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发表时间：
2021-05-17
期刊：
影响因子：
6
通讯作者：
Kunkel TA
中科院分区：
文献类型：
--
作者：
Lujan SA;Kunkel TA
我们描述了DNA错配修复（MMR）的真核细胞核基因组的稳定性，确定全基因组测序的贡献。迄今为止，已知超过40种真核生物的野生型核基因组突变率，而错配修复缺陷生物的测量数量较少，并且集中在酿酒酵母和人类肿瘤上。研究得很好的生物包括果蝇和小家鼠，而遗传学上不太容易处理的物种包括类人猿和长寿的树木。人们已经开发了多种技术来收集每一代或每次细胞分裂的突变率。世代率是通过整个生物体的突变积累实验和通过子代-亲本测序来描述的，或者它们是通过血统来确定的。已经从细胞系突变累积实验、系统性变异等位基因频率和具有已知的每单位组织生长细胞分裂的广泛间隔的样品中估计了每次体细胞分裂的速率。后一种方法也用于估计缺乏专用生殖系的大型生物体（如树木和菌丝真菌）的世代突变率。机制研究涉及MMR基因的遗传操作之前，突变率的测定，迄今仅限于酵母，拟南芥，秀丽隐杆线虫，和一个鸡细胞系。在野生型生物中的大量工作已经开始建立一个合理的基线，但需要更多的工作来揭示真核生物中MMR的多样性。尽管如此，迄今为止报道的少数MMR研究表明，MMR对基因组稳定性的贡献为100倍或更多，并且他们已经发现了使用报告基因测定不可能获得的见解。
We describe the contribution of DNA mismatch repair (MMR) to the stability of the eukaryotic nuclear genome as determined by whole-genome sequencing. To date, wild-type nuclear genome mutation rates are known for over 40 eukaryotic species, while measurements in mismatch repair-defective organisms are fewer in number and are concentrated on Saccharomyces cerevisiae and human tumors. Well-studied organisms include Drosophila melanogaster and Mus musculus, while less genetically tractable species include great apes and long-lived trees. A variety of techniques have been developed to gather mutation rates, either per generation or per cell division. Generational rates are described through whole-organism mutation accumulation experiments and through offspring–parent sequencing, or they have been identified by descent. Rates per somatic cell division have been estimated from cell line mutation accumulation experiments, from systemic variant allele frequencies, and from widely spaced samples with known cell divisions per unit of tissue growth. The latter methods are also used to estimate generational mutation rates for large organisms that lack dedicated germlines, such as trees and hyphal fungi. Mechanistic studies involving genetic manipulation of MMR genes prior to mutation rate determination are thus far confined to yeast, Arabidopsis thaliana, Caenorhabditis elegans, and one chicken cell line. A great deal of work in wild-type organisms has begun to establish a sound baseline, but far more work is needed to uncover the variety of MMR across eukaryotes. Nonetheless, the few MMR studies reported to date indicate that MMR contributes 100-fold or more to genome stability, and they have uncovered insights that would have been impossible to obtain using reporter gene assays.
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影响因子：
64.8
作者：
Behjati, Sam;Huch, Meritxell;van Boxtel, Ruben;Karthaus, Wouter;Wedge, David C.;Tamuri, Asif U.;Martincorena, Inigo;Petljak, Mia;Alexandrov, Ludmil B.;Gundem, Gunes;Tarpey, Patrick S.;Roerink, Sophie;Blokker, Joyce;Maddison, Mark;Mudie, Laura;Robinson, Ben;Nik-Zainal, Serena;Campbell, Peter;Goldman, Nick;van de Wetering, Marc;Cuppen, Edwin;Clevers, Hans;Stratton, Michael R.
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Stratton, Michael R.
影响因子：
5.2
作者：
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影响因子：
2.5
作者：
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影响因子：
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作者：
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通讯作者：
Stratton, M R
影响因子：
30.8
作者：
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通讯作者：
López-Bigas N