DNA repair and ultraviolet mutagenesis in cells from a new patient with xeroderma pigmentosum group G and Cockayne syndrome resemble xeroderma pigmentosum cells
DNA repair and ultraviolet mutagenesis in cells from a new patient with xeroderma pigmentosum group G and Cockayne syndrome resemble xeroderma pigmentosum cells
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DOI：
10.1111/1523-1747.ep12584287
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发表时间：
1996-10-01
影响因子：
6.5
通讯作者：
Kraemer, KH
中科院分区：
文献类型：
--
作者：
Moriwaki, SI;Stefanini, M;Kraemer, KH
着色性干皮病（Xeroderma pigmentosum，XP）/Cockayne综合征（Cockayne syndrome，CS）是一种由两种罕见的遗传性疾病合并而成的综合征。一名对阳光敏感的男孩（XP 20 BE）有严重的CS症状，伴侏儒症、小头畸形、视网膜变性和智力障碍，有XP型色素沉着，6岁时死于明显的恶病质（体重14.5磅）没有皮肤癌，我们评估了他的培养细胞的特征CS或XP DNA修复异常。紫外线（UV）诱导的非程序性DNA合成水平低于正常水平的5%，这是XP切除修复缺陷的特征。细胞融合研究表明，His细胞属于XP互补G组，His细胞对紫外线杀伤敏感，紫外线后RNA合成的恢复率异常低，具有CS和XP的特征，紫外线后pSP 189质粒在His细胞中的存活率明显降低，紫外线后质粒突变频率高于正常细胞，与CS和XP一样，突变质粒标记基因的序列分析显示，与CS一样，具有多个碱基取代的质粒的频率正常，而G：C -> A：T突变的频率异常增加，这是XP的一个特征。有或没有光复活的UV处理的pRSV猫的转染揭示了他的细胞，像XP细胞，不能修复环丁烷嘧啶二聚体或非二聚体的光产物。这些结果表明，XP 20 BE（XP-G/CS）细胞的DNA修复特征在表型上比CS细胞更像XP细胞，而临床上CS表型比XP更突出。
Xeroderma pigmentosum (XP)/Cockayne syndrome (CS) complex is a combination of clinical features of two rare genetic disorders in one individual, A sun-sensitive boy (XP20BE) who had severe symptoms of CS, with dwarfism, microcephaly, retinal degeneration, and mental impairment, had XP-type pigmentation and died at 6 y with marked cachexia (weight 14.5 lb) without skin cancers, We evaluated his cultured cells for characteristic CS or XP DNA-repair abnormalities. The level of ultraviolet (UV)-induced unscheduled DNA synthesis was less than 5% of normal, characteristic of the excision-repair defect of XP. Cell fusion studies indicated that his cells were in XP complementation group G, His cells were hypersensitive to killing by UV, and their post-UV recovery of RNA synthesis was abnormally low, features of both CS and XP, Post-UV survival of plasmid pSP189 in his cells was markedly reduced, and post-UV plasmid mutation frequency was higher than with normal cells, as in both CS and XP, Sequence analysis of the mutated plasmid marker gene showed normal frequency of plasmids with multiple base substitutions, as in CS, and an abnormally increased frequency of G:C --> A:T mutations, a feature of XP. Transfection of UV-treated pRSV cat with or without photoreactivation revealed that his cells, like XP cells, could not repair either cyclobutane pyrimidine dimers or non-dimer photoproducts. These results indicate that the DNA-repair features of the XP20BE (XP-G/CS) cells are phenotypically more like XP cells than CS cells, whereas clinically the CS phenotype is more prominent than XP.