Quiescent murine cells lack global genomic repair but are proficient in transcription-coupled repair
Quiescent murine cells lack global genomic repair but are proficient in transcription-coupled repair
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DOI：
10.1016/j.dnarep.2004.02.010
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发表时间：
2004-07-02
期刊：
影响因子：
3.8
通讯作者：
Heddle, JA
中科院分区：
文献类型：
--
作者：
Bielas, JH;Heddle, JA
体内的大多数细胞，包括干细胞，都处于静止状态，因此大多数DNA损伤发生在静止细胞中。目前还不确定这种损伤是否在静止期被修复或固定为突变，或者两者是否都需要增殖。在转基因小鼠的开发之前，很难区分这两种可能性，因为细胞必须增殖以形成集落，然后才能检测到突变。然而，转基因可以直接从静止的小鼠细胞中穿梭出来，并且可以测量DNA损伤和突变的水平。这种测量表明，在静止细胞中的非转录转基因处不存在突变和修复，尽管当这些细胞被诱导增殖时两者都被启动。相反，转录活性基因的修复独立于相同细胞中的增殖进行，如野生型和XPA（-/-）细胞的差异存活所示。我们从这些结果推断，全球基因组DNA修复（GGR）是不活跃的细胞静止期，但转录偶联修复（TCR），这表明GGR仅限于S，而TCR在整个细胞周期中保持活跃。(C)2004年由Elsevier B. V.出版
The majority of the cells in the body, including stem cells, exist in a quiescent state, so it is in quiescent cells where most DNA damage occurs. It has been uncertain whether or not this damage is repaired or fixed into mutations during quiescence or if proliferation is required for both. Prior to the development of transgenic mice, it was difficult to distinguish between these two possibilities, as cells had to proliferate to form colonies before mutations could be detected. Transgenes, however, can be shuttled out of quiescent mouse cells directly, and the level of DNA damage and mutation can be measured. Such measurements show that both mutation and repair are absent at a non-transcribed transgene in quiescent cells, although both are initiated when these cells are induced to proliferate. Conversely, the repair of transcriptionally active genes proceeds independently of proliferation in the same cells, as shown by the differential survival of wild-type and XPA(-/-) cells. We infer from these results that global genomic DNA repair (GGR) is not active during cellular quiescence but that transcription-coupled repair (TCR) is, suggesting that GGR is restricted to S, whereas TCR remains active throughout the cell cycle. (C) 2004 Published by Elsevier B.V.