Domain structure, localization, and function of DNA polymerase η, defective in xeroderma pigmentosum variant cells
Domain structure, localization, and function of DNA polymerase η, defective in xeroderma pigmentosum variant cells
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DOI：
10.1101/gad.187501
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发表时间：
2001-01-15
影响因子：
10.5
通讯作者：
Lehmann, AR
中科院分区：
文献类型：
--
作者：
Kannouche, P;Broughton, BC;Lehmann, AR
DNA聚合酶eta进行跨损伤合成过去的UV光产物，是缺乏着色性干皮病（XP）的变种。我们报告说，聚合物大多是均匀地定位在细胞核中，但与复制灶在S期。在用紫外线照射或致癌物质处理细胞后，它在DNA损伤时停滞的复制灶处积累。聚合酶活性不需要聚合酶eta的C-末端三分之一。然而，C-末端70个氨基酸需要用于核定位，另外50个氨基酸用于重新定位到病灶中。缺乏这些结构域的Poleta截短不能纠正XP变体细胞中的缺陷。此外，我们已经确定了两个XP变异患者的突变，留下完整的聚合酶基序，但导致本地化结构域的损失。
DNA polymerase eta carries out translesion synthesis past UV photoproducts and is deficient in xeroderma pigmentosum (XP) variants. We report that pol eta is mostly localized uniformly in the nucleus but is associated with replication foci during S phase. Following treatment of cells with UV irradiation or carcinogens, it accumulates at replication foci stalled at DNA damage. The C-terminal third of pol eta is not required for polymerase activity. However, the C-terminal 70 aa are needed for nuclear localization and a further 50 aa for relocalization into foci. Pol eta truncations lacking these domains fail to correct the defects in XP-variant cells. Furthermore, we have identified mutations in two XP variant patients that leave the polymerase motifs intact but cause loss of the localization domains.