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DNA错配修复与癌症。

DNA mismatch repair and cancer.

作者信息

Li Guo-Min

机构信息

Markey Cancer Center and Department of Pathology, University of Kentucky Medical Center, Lexington, KY 40536, USA.

出版信息

Front Biosci. 2003 May 1;8:d997-1017. doi: 10.2741/1121.

Abstract

DNA mismatch repair (MMR) is an important genome caretaker system. It ensures genomic stability by correcting mismatches generated during DNA replication and recombination and by triggering apoptosis of cells with large amounts of DNA damage. Protein components responsible for these reactions are highly conserved through evolution, and homologs of bacterial MutS and MutL, which are key players in the initiation steps of both the strand-specific mismatch correction and MMR-dependent apoptotic signaling, have been identified in human cells. Inactivation of genes encoding these activities leads to genome-wide instability, particularly in simple repetitive sequences, and predisposition to certain types of cancer, including hereditary non-polyposis colorectal cancer.

摘要

DNA错配修复(MMR)是一种重要的基因组维护系统。它通过纠正DNA复制和重组过程中产生的错配,并通过触发大量DNA损伤细胞的凋亡来确保基因组稳定性。负责这些反应的蛋白质成分在进化过程中高度保守,并且在人类细胞中已经鉴定出细菌MutS和MutL的同源物,它们是链特异性错配校正和MMR依赖性凋亡信号传导起始步骤中的关键参与者。编码这些活性的基因失活会导致全基因组不稳定,特别是在简单重复序列中,并易患某些类型的癌症,包括遗传性非息肉病性结直肠癌。

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