DNA methyltransferases, DNA damage repair, and cancer.
DNA methyltransferases, DNA damage repair, and cancer.
复制标题
DOI：
10.1007/978-1-4419-9967-2_1
复制
发表时间：
2013
影响因子：
--
通讯作者：
Robertson, Keith D.
中科院分区：
文献类型：
--
作者：
Jin, Bilian;Robertson, Keith D.
维持DNA甲基转移酶(DNMT)1和从头DNA甲基转移酶DNMT3a和Dnmt3b都是哺乳动物发育所必需的。DNA甲基化是由DNMT催化的，在维持基因组稳定性方面起着重要作用。DNMT的异常表达和DNA甲基化模式的破坏与许多形式的癌症密切相关，尽管这种联系的确切机制仍不清楚。DNA损伤修复系统已经发展成为一种全基因组监测机制，通过识别和修复外源性和内源性DNA损伤来维持染色体的完整性。这些系统的损伤会导致突变，并直接导致肿瘤的发生。越来越多的证据表明，DNMT、DNA甲基化和DNA损伤修复系统之间存在直接联系，这为癌症的发展提供了新的见解。与肿瘤抑制基因(TSG)一样，一系列DNA修复基因经常在多种肿瘤中维持启动子的高甲基化。此外，DNMT1，而不是DNMT3‘S，似乎与DNA损伤修复途径协同发挥作用，以保护细胞免受持续突变事件的影响，这很可能是通过DNA甲基化独立的机制实现的。本章重点回顾DNA甲基化和DNA损伤反应之间的联系。
The maintenance DNA methyltransferase (DNMT) 1 and the de novo methyltransferases DNMT3A and DNMT3B are all essential for mammalian development. DNA methylation, catalyzed by the DNMTs, plays an important role in maintaining genome stability. Aberrant expression of DNMTs and disruption of DNA methylation patterns are closely associated with many forms of cancer, although the exact mechanisms underlying this link remain elusive. DNA damage repair systems have evolved to act as a genome-wide surveillance mechanism to maintain chromosome integrity by recognizing & repairing both exogenous and endogenous DNA insults. Impairment of these systems gives rise to mutations and directly contributes to tumorigenesis. Evidence is mounting for a direct link between DNMTs, DNA methylation, and DNA damage repair systems, which provide new insight into the development of cancer. Like tumor suppressor genes (TSGs), an array of DNA repair genes frequently sustain promoter hypermethylation in a variety of tumors. In addition, DNMT1, but not the DNMT3’s, appear to function coordinately with DNA damage repair pathways to protect cells from sustaining mutagenic events, which is very likely through a DNA methylation-independent mechanism. This chapter is focused on reviewing the links between DNA methylation and the DNA damage response.
登录
查看更多内容
DOI：
10.1073/pnas.2334585100
发表时间：
2003-12-09
影响因子：
11.1
作者：
Cortellino, S;Turner, D;Bellacosa, A
通讯作者：
Bellacosa, A
影响因子：
3.8
作者：
Ai, LB;Quynh, NV;Fan, CY
通讯作者：
Fan, CY
影响因子：
4.8
作者：
Chen, F;Arseven, OK;Cryns, VL
通讯作者：
Cryns, VL
影响因子：
5.6
作者：
Boland, Michael J.;Christman, Judith K.
通讯作者：
Christman, Judith K.
DOI：
10.1073/pnas.0604602103
发表时间：
2006-09-19
影响因子：
11.1
作者：
Egger, Gerda;Jeong, Shinwu;Liang, Gangning
通讯作者：
Liang, Gangning