DNA repair dysfunction in gastrointestinal tract cancers
DNA repair dysfunction in gastrointestinal tract cancers
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DOI：
10.1111/j.1349-7006.2007.00671.x
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发表时间：
2008-03
期刊：
影响因子：
5.7
通讯作者：
Y. Maehara;A. Egashira;E. Oki;Y. Kakeji;T. Tsuzuki
中科院分区：
文献类型：
--
作者：
Y. Maehara;A. Egashira;E. Oki;Y. Kakeji;T. Tsuzuki
DNA修复系统对基因组进行检测，以保持遗传信息，基因组总是暴露于外源性和内源性诱变剂。从原核生物到哺乳动物细胞，这种DNA修复系统的基础是高度保守的，这一事实表明精确的基因组维护机制对生物体的重要性。在过去的15年里，在理解修复过程如何相互作用以及这些机制的破坏如何导致突变和致癌作用的积累方面取得了相当大的进展。1993年，两个研究小组报告说，DNA错配修复可能与遗传性非息肉病性结直肠癌有关，表明DNA修复功能缺陷与癌症之间存在联系。最近，DNA糖基化酶的遗传性疾病，从DNA中去除诱变氧化碱基，已被报道在具有多发性结直肠腺瘤和癌倾向的个体中。这是第一份直接表明氧化DNA修复在人类遗传性癌症中的作用的报告。对基因敲除小鼠的研究已经阐明了这些修复系统在致癌过程中的主要作用。此外，来自癌症患者的临床样本显示了直接参与。本文就细胞内各种DNA修复系统中DNA错配修复和DNA/核苷酸氧化修复的功能作一综述，这两种修复系统在胃肠道肿瘤的发生发展中起着重要作用。（Cancer Sci 2008; 99：451-458）
The DNA repair system surveys the genome, which is always suffering from exposure to both exogenous as well as endogenous mutagens, to maintain the genetic information. The fact that the basis of this DNA repair system is highly conserved, from prokaryote to mammalian cells, suggests the importance of precise genome maintenance mechanisms for organisms. In the past 15 years, considerable progress has been made in understanding how repair processes interact and how disruptions of these mechanisms lead to the accumulation of mutations and carcinogenesis. In 1993, two groups reported that DNA mismatch repair could be associated with hereditary non‐polyposis colorectal cancer, indicating a connection between faulty DNA repair function and cancer. More recently, an inherited disorder of DNA glycosylase, which removes mutagenic oxidized base from DNA, has been reported in individuals with a predisposition to multiple colorectal adenomas and carcinomas. This is the first report that directly indicates the role of the repair of oxidative DNA in human inherited cancer. Studies from gene knockout mice have elucidated the principal role of these repair systems in the process of carcinogenesis. Moreover, clinical samples derived from cancer patients have shown the direct involvement. This review focuses on the function of DNA mismatch repair and oxidative DNA/nucleotide repair among various DNA repair systems in cells, both of which are essentially involved in the carcinogenesis of gastrointestinal tract cancer. (Cancer Sci 2008; 99: 451–458)