Higher-order chromatin structure-dependent repair of DNA double-strand breaks: Involvement of the V(D)J recombination double-strand break repair pathway
Higher-order chromatin structure-dependent repair of DNA double-strand breaks: Involvement of the V(D)J recombination double-strand break repair pathway
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DOI：
10.2307/3579785
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发表时间：
1998-05-01
影响因子：
3.4
通讯作者：
Olive, PL
中科院分区：
文献类型：
--
作者：
Johnston, PJ;MacPhail, SH;Olive, PL
通过对辐射敏感突变体的研究，DNA双链断裂（DSB）的修复与V（D）J重组途径有关。在这里，我们报告了一个可能的关联DSB分布在高阶染色质结构和这一途径。小鼠严重联合免疫缺陷（SCID）细胞和中国仓鼠XR-1细胞均表现出DNA DSB修复缺陷和V（D）J重组缺陷。DSB修复缺陷是不完全的，只有一部分缓慢修复的病变受到这些细胞系突变的影响。我们使用了一种改良的中性过滤器洗脱程序，保留了高阶染色质结构的元素，即核基质-DNA相互作用。在SCID和XR-1细胞中，X射线诱导的DSB在环状DNA结构中以倍数形式发生，是不可修复的。相反，这些病变在放射抗性野生型细胞中得到修复。用含有各自互补基因（XRCC 7和XRCC 4）的人DNA补充的细胞系显示出增加的DSB修复速率。这些结果与先前对xrs 5细胞（XRCC 5组的成员）的发现一致。Xrs 5细胞缺乏V（D）J重组复合物的Ku p80亚基，并显示出与SCID和XR-1细胞相似的修复和V（D）J重组缺陷。(C)1998年，辐射研究会。
Repair of DNA double-strand breaks (DSBs) is linked to the V(D)J recombination pathway through investigations of radiation-sensitive mutants. Here we report a possible association between the distribution of DSBs within higher-order chromatin structures and this pathway. Both murine severe combined immunodeficient (SCID) and Chinese hamster XR-1 cells exhibit defective DNA DSB repair and defective V(D)J recombination. The DSB repair defect is not complete, with only a subset of slowly repairing lesions affected by the mutations in these cell lines. We used a modified neutral filter elution procedure which retained elements of higher-order chromatin structures, namely nuclear matrix-DNA interactions. X-ray-induced DSBs that occurred as multiples within looped DNA structures were nonrepairable in SCID and XR-1 cells. In contrast, these lesions were repaired in radioresistant wild-type cells. Cell lines complemented with human DNA containing the respective complementing genes (XRCC7 and XRCC4) showed an increased rate of DSB repair. These results agree with previous findings with xrs5 cells (a member of the XRCC5 group). Xrs5 cells are defective for the Ku p80 subunit of the V(D)J recombination complex and show repair and V(D)J recombination defects similar to those of SCID and XR-1 cells. (C) 1998 by Radiation Research Society.