PROLIFERATING CELL NUCLEAR ANTIGEN IS REQUIRED FOR DNA EXCISION REPAIR

PROLIFERATING CELL NUCLEAR ANTIGEN IS REQUIRED FOR DNA EXCISION REPAIR
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DOI:
10.1016/0092-8674(92)90416-a
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发表时间:
1992-04-17
期刊:
影响因子:
64.5
通讯作者:
WOOD, RD
WOOD, RD
中科院分区:
生物学1区
文献类型:
--
作者:
SHIVJI, MKK;KENNY, MK;WOOD, RD

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从人类细胞系提取的分离允许核苷酸切除修复受损的DNA被分解成离散的切口和聚合阶段。切割中间产物的产生取决于XP-A蛋白(一种识别受损DNA位点的多肽)和人类单链DNA结合蛋白HSSB。增殖细胞核抗原(PCNA)是DNA合成所必需的,将有缺口的中间产物转化为完整的修复事件。这种对PCNA的需要意味着修复合成是由DNA聚合酶进行的。在缺乏PCNA的情况下,可视化修复中间体的能力促进了多蛋白反应的解剖,该反应导致在细胞防御诱变剂的主要途径中切割受损DNA。
Fractionation of extracts from human cell lines allows nucleotide excision repair of damaged DNA to be resolved into discrete incision and polymerization stages. Generation of incised intermediates depends on the XP-A protein, a polypeptide that recognizes sites of damaged DNA, and on the human single-stranded DNA-binding protein HSSB. The proliferating cell nuclear antigen (PCNA) is required for the DNA synthesis that converts the nicked intermediates to completed repair events. This need for PCNA implies that repair synthesis is carried out by DNA polymerase-delta or epsilon. The ability to visualize repair intermediates in the absence of PCNA facilitates dissection of the multiprotein reaction that leads to incision of damaged DNA in a major pathway of cellular defense against mutagens.