THE RELATIONSHIP BETWEEN SISTER-CHROMATID EXCHANGE AND PERTURBATIONS IN DNA-REPLICATION IN MUTANT EM9 AND NORMAL CHO CELLS
THE RELATIONSHIP BETWEEN SISTER-CHROMATID EXCHANGE AND PERTURBATIONS IN DNA-REPLICATION IN MUTANT EM9 AND NORMAL CHO CELLS
复制标题
DOI：
10.1016/0027-5107(83)90053-2
复制
发表时间：
1983-01-01
期刊：
影响因子：
--
通讯作者：
CARRANO, AV
中科院分区：
文献类型：
--
作者：
DILLEHAY, LE;THOMPSON, LH;CARRANO, AV
在CHO突变株系EM 9中发生的大多数高（升高12倍）基线姐妹染色单体交换（SCE）似乎是掺入BrdUrd [5-溴-2“-脱氧尿苷]的结果，并且它们在模板链中含有BrdUrd的DNA复制期间出现。在正常的CHO细胞中，与在未取代的模板上复制期间观察到的那些相比，在含BrdUrd的模板上新复制的DNA的碱性洗脱模式显著改变。在这样一个改变的模板上合成的新生DNA在达到成熟尺寸时被延迟，这可能是因为复制叉在沿模板沿着随机出现的位点被暂时阻断。复制叉的暂时阻塞可能是SCE的先决条件。在BrdUrd取代的模板上复制的延迟在EM 9细胞中比在亲本AA 8细胞中更大，并且在用苯甲酰胺（聚（ADPR [ADP-核糖]）聚合酶的抑制剂）处理的AA 8细胞中也比在未处理的AA 8细胞中更大。在这些条件下，用苯甲酰胺处理也使AA 8的SCE增加了7倍。具有低基线SCE频率的EM 9衍生的回复突变株系在BrdUrd取代的模板上的复制延迟比EM 9少。在模板链含有CldUrd [5-氯-2“-脱氧尿苷]的条件下，在AA 8细胞中，CldUrd [5-氯-2”-脱氧尿苷]产生的SCE是BrdUrd的4倍，在CldUrd取代的细胞中，AA 8的复制延迟并没有更大。除了延迟的其他因素似乎参与SCE的生产由卤素取代的嘧啶分子的掺入导致的模板病变。
The majority of the high (12-fold elevated) baseline sister-chromatid exchanges (SCE) that occur in the CHO mutant line EM9 appear to be a consequence of incorporated BrdUrd [5-bromo-2''-deoxyuridine], and they arise during replication of DNA containing BrdUrd in a template strand. In normal CHO cells the alkaline elution patterns of DNA newly replicated on a BrdUrd-containing template are significantly altered compared with those seen during the replication on an unsubstituted template. The nascent DNA synthesized on such an altered template is delayed in reaching mature size, possibly because replication forks are temporarily blocked at sites occurring randomly along the template. Transient blockage of replication forks may be a prerequisite for SCE. The delay in replication on BrdUrd-substituted templates was greater in EM9 cells than in parental AA8 cells and was also greater in AA8 cells treated with benzamide, an inhibitor of poly(ADPR [ADP-ribose]) polymerase, than in untreated AA8 cells. Under these conditions, treatment with benzamide also produced a 7-fold increase in SCE in AA8. An EM9-derived revertant line that has a low baseline SCE frequency showed less delay in replication on BrdUrd-substituted templates than did EM9. Under conditions where the template strand contained CldUrd [5-chloro-2''-deoxyuridine], which was shown to produce 4-fold more SCE than BrdUrd in AA8 cells, the replication delay in AA8 was not any greater in the CldUrd-substituted cells. Other factors besides the delay appear to be involved in the production of SCE by the template lesions resulting from incorporation of the halogen-substituted pyrimidine molecules.