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To prevent the damage caused by DNA strand breaks, eukaryotic cells have evolved a series of highly conserved DNA repair mechanisms.
The ubiquitously expressed acetyltransferase, Tip60, plays a central role in ATM (ataxia-telangiectasia mutated) activation
which is involved in DNA repair. Recent work uncovered a new mechanism of ATM activation mediated by Tip60 and demonstrated
that histone methylation, specifically, trimethylation of histone H3, is a key factor in the process. Here, we review the
current understanding of how Tip60 is activated and how it activates ATM in response to DNA damage. 相似文献
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Dynamic protein methylation in chromatin biology 总被引:1,自引:1,他引:0
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A. Shukla P. Chaurasia S. R. Bhaumik 《Cellular and molecular life sciences : CMLS》2009,66(8):1419-1433
Methylation of lysine residues of histones is associated with functionally distinct regions of chromatin, and, therefore,
is an important epigenetic mark. Over the past few years, several enzymes that catalyze this covalent modification on different
lysine residues of histones have been discovered. Intriguingly, histone lysine methylation has also been shown to be cross-regulated
by histone ubiquitination or the enzymes that catalyze this modification. These covalent modifications and their cross-talks
play important roles in regulation of gene expression, heterochromatin formation, genome stability, and cancer. Thus, there
has been a very rapid progress within past several years towards elucidating the molecular basis of histone lysine methylation
and ubiquitination, and their aberrations in human diseases. Here, we discuss these covalent modifications with their cross-regulation
and roles in controlling gene expression and stability.
Received 24 September 2008; received after revision 21 November 2008; accepted 28 November 2008 相似文献
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代葳 《辽宁大学学报(自然科学版)》2006,33(4):353-357
介绍了在卵巢癌的发展和治疗中表观遗传学的重要性,特别强调了在卵巢癌中内源性和获得性耐药性遗传途径中异常的DNA甲基化和组蛋白去乙酰化的重要性.通过表观遗传治疗反转肿瘤抑制基因沉寂和其他参与药物级联反应的基因沉寂为出现耐药性的卵巢癌患者带来了新的希望. 相似文献
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Summary A modified radioimmunoprecipitation technique is described which allows the specific detection of histone H2A antigens. The technique circumvents unspecific binding of histones to the bacterial adsorbent. 相似文献
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核小体是染色质的基本结构单位,核小体组蛋白N末端尾部可以发生甲基化、乙酰化等多种共价修饰.组蛋白密码假设多种组蛋白修饰以组合方式发挥作用.自组蛋白密码假设被提出后,组蛋白修饰组合模式成为表观遗传学领域的重要研究内容.在染色质免疫沉淀基因芯片和免疫沉淀高通量测序等相关实验数据的基础上,多种算法被用于研究组蛋白修饰的组合.文章介绍了组蛋白修饰的发生、位点、相关修饰酶以及生物学功能,对组蛋白修饰组合以及与基因表达关系的研究进行了总结,同时对组蛋白修饰组合模式一些适用的研究方法做了概述和分析. 相似文献
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Aging appears to be an irreversible process. Here we report that nicotinamide (NAA) can induce rapid and reversible reversion
of aging phenotypes in human diploid fibroblasts in terms of cell morphology and senescence-associated β-galactosidase activity.
Although NAA seems to enhance the replicative potential of the cells, it has little effect on their growth rate and life span,
suggesting that NAA action is rather separated from the cellular replicative system. The effects are unique to NAA: none of
the NAA-related compounds examined (an NAD precursor/niacin, NAD analogs, and poly(ADP-ribose) polymerase inhibitors) exerted
similar effects. Thus, NAD-related metabolism and poly(ADP-ribosyl)ation are unlikely related to the NAA action. On the other
hand, histone acetyltransferase (HAT) activity was elevated in NAA-exposed cells, while in aged cells, HAT activity and histone
H4 acetylation were lowered. Taken together, the results suggest that NAA may cause rejuvenation by restoring, at least in
part, altered gene expression in aged cells through its activation of HAT.
Received 27 August 2001; received after revision 15 October 2001; accepted 15 October 2001 相似文献
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组蛋白甲基化修饰对遗传信息解读有着重要影响,是表观遗传调控的主要机制之一。组蛋白甲基化可以被一类称作"阅读器"的结构域所特异识别并介导下游生物学事件。本文综述了目前已知的组蛋白甲基化阅读器(包括"皇室家族"成员、PHD锌指及BAH 等结构域)的结构特征及其对于甲基化修饰位点和程度特异性识别的分子基础。另外,探讨了表观遗传修饰调控中的组合识别、修饰对话等概念与机制。 相似文献