The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase η
The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase η
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DOI：
10.1038/21447
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发表时间：
1999-06-17
期刊：
影响因子：
64.8
通讯作者：
Hanaoka, F
中科院分区：
文献类型：
--
作者：
Masutani, C;Kusumoto, R;Hanaoka, F
着色性干皮变异体（XP-V）是一种遗传性疾病，与阳光诱导的皮肤癌发病率增加有关。与其他着色性干皮细胞（属于XP-A至XP-G组）不同，XP-V细胞进行正常的核苷酸切除修复过程，但在复制紫外线损伤的DNA方面存在缺陷（1,2）。一段时间以来，人们一直怀疑XPV基因编码一种参与跨病变DNA合成的蛋白质；我们最近从HeLa细胞中分离出一种DNA聚合酶，该酶可以绕过XP-V细胞提取物中紫外线诱导的胸腺嘧啶二聚体，继续在受损DNA上进行复制(3)。在这里，我们发现这种聚合酶是酵母Rad30蛋白的人类同源物，最近被鉴定为DNA聚合酶eta（参考文献4）。该聚合酶和酵母Rad30是损伤旁路复制蛋白家族的成员（5-10），该家族包括大肠杆菌蛋白UmuC和DinB以及酵母Rev1蛋白。我们发现所有被检测的XP-V细胞都携带DNA聚合酶eta基因突变。重组人DNA聚合酶通过绕过受损DNA上的胸腺嘧啶二聚体，纠正了XP-V细胞提取物无法进行DNA复制的缺陷。这些结果表明DNA聚合酶eta可能是XPV基因的产物。
Xeroderma pigmentosum variant (XP-V) is an inherited disorder which is associated with increased incidence of sunlight-induced skin cancers, Unlike other xeroderma pigmentosum cells (belonging to groups XP-A to XP-G), XP-V cells carry out normal nucleotide-excision repair processes but are defective in their replication of ultraviolet-damaged DNA(1,2). It has been suspected for some time that the XPV gene encodes a protein that is involved in trans-lesion DNA synthesis; but the gene product has never been isolated Using an improved cell-free assay for trans-lesion DNA synthesis, we have recently isolated a DNA polymerase from HeLa cells that continues replication on damaged DNA by bypassing ultraviolet-induced thymine dimers in XP-V cell extracts(3). Here we show that this polymerase is a human homologue of the yeast Rad30 protein, recently identified as DNA polymerase eta (ref. 4). This polymerase and yeast Rad30 are members of a family of damage-bypass replication proteins(5-10) which comprises the Escherichia coli proteins UmuC and DinB and the yeast Rev1 protein. We found that all XP-V cells examined carry mutations in their DNA polymerase eta gene. Recombinant human DNA polymerase eta corrects the inability of XP-V cell extracts to carry out DNA replication by bypassing thymine dimers on damaged DNA. Together these results indicate that DNA polymerase eta could be the XPV gene product.