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人类单链DNA结合蛋白HSSB/RPA在核苷酸切除修复早期阶段的作用。

A role for the human single-stranded DNA binding protein HSSB/RPA in an early stage of nucleotide excision repair.

作者信息

Coverley D, Kenny M K, Lane D P, Wood R D

机构信息

Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, Herts, UK.

出版信息

Nucleic Acids Res. 1992 Aug 11;20(15):3873-80. doi: 10.1093/nar/20.15.3873.

DOI:10.1093/nar/20.15.3873
PMID:1508673
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC334061/
Abstract

The human single-stranded DNA binding protein (HSSB/RPA) is involved in several processes that maintain the integrity of the genome including DNA replication, homologous recombination, and nucleotide excision repair of damaged DNA. We report studies that analyze the role of HSSB in DNA repair. Specific protein-protein interactions appear to be involved in the repair function of HSSB, since it cannot be replaced by heterologous single-stranded DNA binding proteins. Anti-HSSB antibodies that inhibit the ability of HSSB to stimulate DNA polymerase alpha also inhibit repair synthesis mediated by human cell-free extracts. However, antibodies that neutralize DNA polymerase alpha do not inhibit repair synthesis. Repair is sensitive to aphidicolin, suggesting that DNA polymerase epsilon or delta participates in nucleotide excision repair by cell extracts. HSSB has a role other than generally stimulating synthesis by DNA polymerases, as it does not enhance the residual damage-dependent background synthesis displayed by repair-deficient extracts from xeroderma pigmentosum cells. Significantly, when damaged DNA is incised by the Escherichia coli UvrABC repair enzyme, human cell extracts can carry out repair synthesis even when HSSB has been neutralized with antibodies. This suggests that HSSB functions in an early stage of repair, rather than exclusively in repair synthesis. A model for the role of HSSB in repair is presented.

摘要

人类单链DNA结合蛋白（HSSB/RPA）参与了多个维持基因组完整性的过程，包括DNA复制、同源重组以及受损DNA的核苷酸切除修复。我们报告了分析HSSB在DNA修复中作用的研究。特定的蛋白质-蛋白质相互作用似乎参与了HSSB的修复功能，因为它不能被异源单链DNA结合蛋白所取代。抑制HSSB刺激DNA聚合酶α能力的抗HSSB抗体也会抑制人无细胞提取物介导的修复合成。然而，中和DNA聚合酶α的抗体并不抑制修复合成。修复对阿非迪霉素敏感，这表明DNA聚合酶ε或δ参与了细胞提取物的核苷酸切除修复。HSSB除了一般地刺激DNA聚合酶的合成外还有其他作用，因为它不会增强色素性干皮病细胞修复缺陷提取物所显示的依赖于残留损伤的背景合成。值得注意的是，当受损DNA被大肠杆菌UvrABC修复酶切割时，即使HSSB已被抗体中和，人细胞提取物仍能进行修复合成。这表明HSSB在修复的早期阶段起作用，而不是仅在修复合成中起作用。本文提出了一个HSSB在修复中作用的模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96e5/334061/00125d74f523/nar00226-0075-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96e5/334061/6425f2ef9861/nar00226-0073-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96e5/334061/9145248abd31/nar00226-0073-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96e5/334061/174256ea3540/nar00226-0073-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96e5/334061/892edd06681a/nar00226-0075-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96e5/334061/00125d74f523/nar00226-0075-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96e5/334061/6425f2ef9861/nar00226-0073-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96e5/334061/9145248abd31/nar00226-0073-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96e5/334061/174256ea3540/nar00226-0073-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96e5/334061/892edd06681a/nar00226-0075-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96e5/334061/00125d74f523/nar00226-0075-b.jpg

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