Every microsatellite is different: Intrinsic DNA features dictate mutagenesis of common microsatellites present in the human genome.
Every microsatellite is different: Intrinsic DNA features dictate mutagenesis of common microsatellites present in the human genome.
复制标题
每个微卫星都不同：内在的DNA特征决定了人类基因组中存在的常见微卫星的诱变。
DOI：
10.1002/mc.20499
复制
发表时间：
2009-04
影响因子：
4.6
通讯作者：
Hile, Suzanne E.
中科院分区：
文献类型：
--
作者：
Eckert, Kristin A.;Hile, Suzanne E.
关键词：
微卫星序列普遍存在于人类基因组中，是基因组功能的重要调控因子。在这里，我们研究的突变机制，高度丰富的单，双，和四核苷酸微卫星的稳定性。根据系谱分析和实验模型估计的微卫星突变率范围从每代每个位点的100 -6突变到100 -2突变不等。绝大多数观察到的突变变异可归因于等位基因本身固有的特征，包括基序大小、长度和序列组成。在几个模型系统中已经观察到基序长度和诱变之间的大于线性的关系。基序序列差异对人类细胞突变率中观察到的变异贡献高达10倍。微卫星突变的主要机制是DNA合成过程中的链滑移。DNA聚合酶在微卫星内产生错误的频率比编码序列中的移码频率高10至100倍。模体序列显着影响聚合酶错误率和特异性，导致互补微卫星内的链偏差。重要的是，微卫星内的聚合酶错误包括碱基替换、缺失和复杂突变，所有这些都从纯微卫星产生中断的等位基因。复制后错配修复效率受微卫星基序大小和序列的影响，也有助于观察到的微卫星突变的变化。常见微卫星内DNA合成的抑制是高度序列依赖性的，并且与错误的产生正相关。常见微卫星内的DNA二级结构可以解释一些DNA聚合酶暂停位点，并且可能是影响突变特异性的重要因素。
Microsatellite sequences are ubiquitous in the human genome and are important regulators of genome function. Here, we examine the mutational mechanisms governing the stability of highly abundant mono-, di-, and tetranucleotide microsatellites. Microsatellite mutation rate estimates from pedigree analyses and experimental models range from a low of ∼10-6 to a high of ∼10-2 mutations per locus per generation. The vast majority of observed mutational variation can be attributed to features intrinsic to the allele itself, including motif size, length, and sequence composition. A greater than linear relationship between motif length and mutagenesis has been observed in several model systems. Motif sequence differences contribute up to 10-fold to variation observed in human cell mutation rates. The major mechanism of microsatellite mutagenesis is strand slippage during DNA synthesis. DNA polymerases produce errors within microsatellites at a frequency that is 10- to 100-fold higher than the frequency of frameshifts in coding sequences. Motif sequence significantly affects both polymerase error rate and specificity, resulting in strand biases within complementary microsatellites. Importantly, polymerase errors within microsatellites include base substitutions, deletions and complex mutations, all of which produced interrupted alleles from pure microsatellites. Postreplication mismatch repair efficiency is affected microsatellite motif size and sequence, also contributing to the observed variation in microsatellite mutagenesis. Inhibition of DNA synthesis within common microsatellites is highly sequence-dependent, and is positively correlated with the production of errors. DNA secondary structure within common microsatellites can account for some DNA polymerase pause sites, and may be an important factor influencing mutational specificity.
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影响因子：
30.8
作者：
CHU, CS;TRAPNELL, BC;CRYSTAL, RG
通讯作者：
CRYSTAL, RG
影响因子：
7
作者：
Kelkar, Yogeshwar D.;Tyekucheva, Svitlana;Makova, Kateryna D.
通讯作者：
Makova, Kateryna D.
影响因子：
9.8
作者：
Brinkmann, B;Klintschar, M;Rolf, B
通讯作者：
Rolf, B
DOI：
10.1073/pnas.95.18.10774
发表时间：
1998-09-01
影响因子：
11.1
作者：
Kruglyak, S;Durrett, RT;Aquadro, CF
通讯作者：
Aquadro, CF
影响因子：
11.4
作者：
Hui, JY;Hung, LH;Bindereif, A
通讯作者：
Bindereif, A