DNA repair in differentiated cells: Some new answers to old questions
DNA repair in differentiated cells: Some new answers to old questions
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DOI：
10.1016/j.neuroscience.2006.07.006
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发表时间：
2007-04-14
期刊：
影响因子：
3.3
通讯作者：
Nouspikel, T.
中科院分区：
文献类型：
--
作者：
Nouspikel, T.
最终分化的细胞不需要复制它们的基因组，因此可能省去了维持几个修复系统来不断扫描它们的整个DNA补体的艰巨任务。显然，转录后的基因需要修复，细胞才能发挥其特化功能，而转录偶联修复和分化相关修复等专用机制可以确保这些转录活性结构域的维持。许多研究小组对分化细胞中的DNA修复进行了研究，但往往得出不同的结果，这可能是因为分化细胞有不同的类别，具有独特的性质。因此，神经元应该持续一生，而肌细胞是由前体细胞支持的，而像巨噬细胞这样的白细胞是不断被替换的。更重要的是，不同的DNA修复系统对细胞分化的反应可能不同，这可能取决于它们是否能与转录结合。核苷酸切除修复（NER）可能是最通用的DNA修复系统，并与转录偶联。在包括神经元在内的几种细胞类型中，NER被证明通过分化而减弱。这种衰减只发生在全球基因组水平，转录的基因仍然被有效地修复。我们已经确定，这种衰减是由于缺乏一个NER因子的泛素化，很可能是由于泛素活化酶Ell的磷酸化差异。由于人类细胞中只有一个E1，其他代谢途径很可能也受到类似的影响，这取决于它们是否依赖于对E1磷酸化状态敏感的E2酶。(c) 2006 ibro。Elsevier Ltd.出版。版权所有。
Terminally differentiated cells need never replicate their genomes and may therefore dispense with the daunting task of maintaining several repair systems to constantly scan their entire complement of DNA. Obviously, transcribed genes need to be repaired, so that cells can carry out their specialized functions, but dedicated mechanisms such as transcription-coupled repair and differentiation-associated repair can ensure the maintenance of those transcriptionally active domains. Many groups have studied DNA repair in differentiated cells, often with divergent results, possibly because there are distinct classes of differentiated cells, with unique properties. Thus neurons ought to last for a lifetime, whereas myocytes are backed by precursor cells, while white blood cells like macrophages are constantly being replaced. More importantly, different DNA repair systems can vary in their response to cellular differentiation, possibly depending on whether they can be coupled to transcription. Nucleotide excision repair (NER) is probably the most versatile DNA repair system and is coupled to transcription. NER was shown to be attenuated by differentiation in several cell types, including neurons. The attenuation occurs only at the global genome level, with transcribed genes still being efficiently repaired. We have determined that this attenuation results from the lack of ubiquitination of a NER factor, most likely owing to differences in phosphorylation of the ubiquitin-activating enzyme Ell. Because there is only one E1 in human cells, it is likely that other metabolic pathways are similarly affected, depending on whether they rely on an E2 enzyme which is sensitive to the state of E1 phosphorylation. (C) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.