摘要翻译：
从正常细胞到癌细胞的转变需要许多高度特异性的突变，这些突变影响细胞周期调节、凋亡、分化和许多其他细胞功能。癌症基因组的一个特点是基因组的不稳定性，突变率远远高于正常细胞。在微卫星不稳定性（MIN肿瘤）中，这些通常是由错配修复基因的损伤引起的，允许基因组的进一步突变和肿瘤的进展。这些突变率可能接近于适应性RNA基因组准种模型中发现的错误突变，这表明进一步增加突变率将破坏癌变基因组。然而，最近的结果表明，DNA基因组在突变率上表现出远低于保守对应体的错误阈值。此外，当保守系统中的最大可行突变率随着主序列适应度的增加而无限增加时，半保留阈值则稳定在一个相对较低的值。这意味着一个悖论，其中不可接近的突变率在存活的肿瘤细胞中被发现。在本文中，我们解决了这个悖论，证明了保守复制(RNA)准种模型和半保留(DNA)模型之间的同构性，甲基化后DNA修复机制受损。因此，当DNA修复失活时，最大可行突变率平稳地增加到转化景观上保守复制系统的最大可行突变率，其上限取决于复制率。我们假定甲基化后修复机制的失活是肿瘤细胞进展的基础，因此这些机制作为预防和破坏癌症基因组的一种方法。
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英文标题：
《The Importance of DNA Repair in Tumor Suppression》
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作者：
Yisroel Brumer and Eugene I. Shakhnovich
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最新提交年份：
2004
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分类信息：

一级分类：Quantitative Biology        数量生物学
二级分类：Genomics        基因组学
分类描述：DNA sequencing and assembly; gene and motif finding; RNA editing and alternative splicing; genomic structure and processes (replication, transcription, methylation, etc); mutational processes.
DNA测序与组装；基因和基序的发现；RNA编辑和选择性剪接；基因组结构和过程（复制、转录、甲基化等）；突变过程。
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一级分类：Physics        物理学
二级分类：Other Condensed Matter        其他凝聚态物质
分类描述：Work in condensed matter that does not fit into the other cond-mat classifications
在不适合其他cond-mat分类的凝聚态物质中工作
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一级分类：Quantitative Biology        数量生物学
二级分类：Other Quantitative Biology        其他定量生物学
分类描述：Work in quantitative biology that does not fit into the other q-bio classifications
不适合其他q-bio分类的定量生物学工作
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英文摘要：
  The transition from a normal to cancerous cell requires a number of highly specific mutations that affect cell cycle regulation, apoptosis, differentiation, and many other cell functions. One hallmark of cancerous genomes is genomic instability, with mutation rates far greater than those of normal cells. In microsatellite instability (MIN tumors), these are often caused by damage to mismatch repair genes, allowing further mutation of the genome and tumor progression. These mutation rates may lie near the error catastrophe found in the quasispecies model of adaptive RNA genomes, suggesting that further increasing mutation rates will destroy cancerous genomes. However, recent results have demonstrated that DNA genomes exhibit an error threshold at mutation rates far lower than their conservative counterparts. Furthermore, while the maximum viable mutation rate in conservative systems increases indefinitely with increasing master sequence fitness, the semiconservative threshold plateaus at a relatively low value. This implies a paradox, wherein inaccessible mutation rates are found in viable tumor cells. In this paper, we address this paradox, demonstrating an isomorphism between the conservatively replicating (RNA) quasispecies model and the semiconservative (DNA) model with post-methylation DNA repair mechanisms impaired. Thus, as DNA repair becomes inactivated, the maximum viable mutation rate increases smoothly to that of a conservatively replicating system on a transformed landscape, with an upper bound that is dependent on replication rates. We postulate that inactivation of post-methylation repair mechanisms are fundamental to the progression of a tumor cell and hence these mechanisms act as a method for prevention and destruction of cancerous genomes.
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PDF链接：
https://arxiv.org/pdf/q-bio/0403018