Bryant P E
School of Biomedical Sciences, University of St Andrews, Scotland, UK.
Int J Radiat Biol. 1998 Mar;73(3):243-51. doi: 10.1080/095530098142338.
To present and evaluate the 'signal' model for the formation of radiation-induced chromatid breaks.
Chromatid breaks in human cells represent the apparent interstitial loss of up to about 40 Mbp of DNA, difficult to account for as single lesions under the classical 'breakage-and-reunion' hypothesis. If breakage-first resulted from two interacting DNA double-strand breaks (dsb) with the loss or displacement of the intervening fragment, a dose-squared relationship would be predicted for chromatid breaks. However, the relationship between chromatid break frequency and dose for human cells is linear. The alternative 'exchange' model of Revell is based on the principle of the interaction of two initiating lesions, thus also predicting a dose-squared relationship for chromatid 'breaks'. The signal model explains the conversion of dsb into chromatid breaks on the assumption that a single dsb generates a signal which triggers the cell to initiate a recombinational exchange involving a large loop of chromatin. Incomplete exchanges would be observed as chromatid breaks. Possible candidates for the signalling molecule(s) are DNA protein kinase (DNA PK) and the ATM protein.
提出并评估辐射诱导染色单体断裂形成的“信号”模型。
人类细胞中的染色单体断裂表现为高达约40兆碱基对DNA的明显间质丢失，在经典的“断裂-重连”假说下，难以将其解释为单个损伤。如果断裂首先是由两个相互作用的DNA双链断裂（dsb）导致中间片段丢失或移位，那么染色单体断裂将呈现剂量平方关系。然而，人类细胞中染色单体断裂频率与剂量之间的关系是线性的。Revell的另一种“交换”模型基于两个起始损伤相互作用的原理，因此也预测染色单体“断裂”呈剂量平方关系。信号模型假设单个dsb产生一个信号，该信号触发细胞启动涉及大染色质环的重组交换，从而解释dsb向染色单体断裂的转化。不完全交换将表现为染色单体断裂。信号分子的可能候选者是DNA蛋白激酶（DNA PK）和ATM蛋白。
