Poly(ADP-ribose)polymerase: A guardian of the genome that facilitates DNA repair by protecting against DNA recombination
Poly(ADP-ribose)polymerase: A guardian of the genome that facilitates DNA repair by protecting against DNA recombination
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DOI：
10.1023/a:1006983304079
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发表时间：
1999-03-01
影响因子：
4.3
通讯作者：
Berger, NA
中科院分区：
文献类型：
--
作者：
Chatterjee, S;Berger, SJ;Berger, NA
我们研究了中国仓鼠V79细胞及其衍生细胞系ADPRT54和ADPRT351对X射线和MNNG的克隆存活反应。在指数生长条件下，与亲本V79细胞相比，两种PARP缺陷细胞系对X射线和MNNG都高度敏感。相反，在生长受阻、融合的条件下，V79和PARP缺陷细胞对X射线和MNNG的敏感性相似，这表明PARP可能参与对数生长细胞中X射线或MNNG诱导的DNA损伤的修复，但在生长受阻的融合细胞中不参与。然而，这一建议造成了一个两难境地，即PARP如何在所有生长阶段都功能活跃的情况下，仅在选定的生长阶段参与DNA修复。为了解释这些矛盾的结果并解决这一困境，我们提出了一个假设，该假设基于一致的观察，即抑制PARP会导致姐妹染色单体交换(SCES)显着增加。因此，我们认为PARP是基因组的守护者，可以防止DNA重组。我们扩展了这个主题，为我们的结果和其他许多人的研究提供了解释。
We have studied the clonogenic survival response to X-rays and MNNG of V79 Chinese hamster cells and two derivative cell lines, ADPRT54 and ADPRT351, deficient in poly(ADP-ribose) polymerase (PARP) activity. Under conditions of exponential growth, both PARP-deficient cell lines are hypersensitive to X-rays and MNNG compared to their parental V79 cells. Ln contrast, under growth arrested, confluent conditions, V79 and PARP-deficient cells become similarly sensitive to X-rays and MNNG suggesting that PARP may be involved in the repair of X-ray or MNNG-induced DNA damage in logarithmically growing cells but not in growth-arrested confluent cells. This suggestion, however, creates a dilemma as to how PARP can be involved in DNA repair in only selected growth phases while it is functionally active in all growth phases. To explain these paradoxical results and resolve this dilemma we propose a hypothesis based on the consistent observation that inhibition of PARP results in a significant increase in sister chromatid exchange (SCEs). Thus, we propose that PARP is a guardian of the genome that protects against DNA recombination. We have extended this theme to provide an explanation for our results and the studies done by many others.