TRANSCRIPTION-COUPLED REPAIR REMOVES BOTH CYCLOBUTANE PYRIMIDINE DIMERS AND 6-4-PHOTOPRODUCTS WITH EQUAL EFFICIENCY AND IN A SEQUENTIAL WAY FROM TRANSCRIBED DNA IN XERODERMA-PIGMENTOSUM GROUP-C FIBROBLASTS
TRANSCRIPTION-COUPLED REPAIR REMOVES BOTH CYCLOBUTANE PYRIMIDINE DIMERS AND 6-4-PHOTOPRODUCTS WITH EQUAL EFFICIENCY AND IN A SEQUENTIAL WAY FROM TRANSCRIBED DNA IN XERODERMA-PIGMENTOSUM GROUP-C FIBROBLASTS
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DOI：
10.1002/j.1460-2075.1995.tb07010.x
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发表时间：
1995-01-16
期刊：
影响因子：
11.4
通讯作者：
MULLENDERS, LHF
中科院分区：
文献类型：
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作者：
VANHOFFEN, A;VENEMA, J;MULLENDERS, LHF
我们研究了全球和转录偶联核苷酸切除修复途径的结构不同的DNA损伤的去除的贡献。在正常人成纤维细胞和着色性干皮病C组（XP-C）成纤维细胞中测定了UV诱导的环丁烷嘧啶二聚体（CPD）和嘧啶（6-4）嘧啶酮光产物（6-4PPs）的活性和非活性基因的修复动力学。以前我们已经表明，在暴露于10 J/cm（2）紫外线剂量的正常人体细胞中，CPD的修复通过两种途径进行：全局修复和转录偶联修复，后者负责加速活性基因转录链中CPD的修复。到目前为止，还没有明确的证据表明6- 4PP的转录偶联修复。在这里，我们证明了6- 4PP确实形成了转录偶联修复的靶点。在XP-C细胞中，暴露于30 J/m2并且仅能够进行转录偶联修复，CPD以及6- 4PP被选择性地从腺苷脱氨酶（ADA）基因的转录链中去除，并且具有相似的动力学。ADA基因的非转录链和失活的754基因几乎不被修复。与XP-C细胞相反，暴露于30 J/m2的正常细胞缺乏6- 4PP和CPD的链特异性修复，这表明转录偶联修复被全局修复所取代，可能是由于在这种高UV剂量下严重抑制转录。6-4PPs在正常细胞中的修复速度比CPD快得多，这可能与整体修复系统对前者损伤的亲和力更高有关。在XP-C细胞中，在30 J/m（2）时转录链中6- 4PP和CPD的修复速率相似，表明光损伤的转录偶联修复以顺序方式发生。我们的研究结果强烈表明，转录偶联修复去除病变的意义取决于病变的类型和剂量。
We investigated the contribution of the global and the transcription-coupled nucleotide excision repair pathway to the removal of structurally different DNA lesions. The repair kinetics of UV-induced cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs) were determined in an active and inactive gene in normal human fibroblasts and in xeroderma pigmentosum group C (XP-C) fibroblasts. Previously we have shown that in normal human cells exposed to a UV dose of 10 J/cm(2) repair of CPDs takes place via two pathways: global repair and transcription-coupled repair, the latter being responsible for accelerated repair of CPDs in the transcribed strand of active genes. So far, no clear evidence for transcription-coupled repair of 6-4PPs has been presented. Here we demonstrate that 6-4PPs really form a target for transcription-coupled repair. In XP-C cells, exposed to 30 J/m(2) and only capable of performing transcription-coupled repair, CPDs as well as 6-4PPs are removed selectively and with similar kinetics from the transcribed strand of the adenosine deaminase (ADA) gene. The non-transcribed strand of the ADA gene and the inactive 754 gene are hardly repaired. In contrast to XP-C cells, normal cells exposed to 30 J/m(2) lack strand-specific repair of both 6-4PPs and CPDs, suggesting that transcription-coupled repair is overruled by global repair, probably due to severe inhibition of transcription at this high UV dose. The much more rapid repair of 6-4PPs compared with CPDs in normal cells may be related to higher affinity of the global repair system for the former lesion. In XP-C cells the similarity of the rate of repair of both 6-4PPs and CPDs in the transcribed strand at 30 J/m(2) indicates that transcription-coupled repair of photolesions takes place in a sequential way. Our results strongly suggest that the significance of transcription-coupled repair for removal of lesions depends on the type of lesion and on the dose employed.