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高迁移率族蛋白B1（HMGB1）与人类拓扑异构酶IIα相互作用并刺激其催化活性。

HMGB1 interacts with human topoisomerase IIalpha and stimulates its catalytic activity.

作者信息

Stros Michal, Bacíková Alena, Polanská Eva, Stokrová Jitka, Strauss François

机构信息

Laboratory of Analysis of Chromosomal Proteins, Academy of Sciences of the Czech Republic, Institute of Biophysics, Brno, Czech Republic.

出版信息

Nucleic Acids Res. 2007;35(15):5001-13. doi: 10.1093/nar/gkm525. Epub 2007 Jul 18.

DOI:10.1093/nar/gkm525
PMID:17636313
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1976466/
Abstract

DNA topoisomerase IIalpha (topo IIalpha) is an essential nuclear enzyme and its unique decatenation activity has been implicated in many aspects of chromosome dynamics such as chromosome replication and segregation during mitosis. Here we show that chromatin-associated protein HMGB1 (a member of the large family of HMG-box proteins with possible functions in DNA replication, transcription, recombination and DNA repair) promotes topo IIalpha-mediated catenation of circular DNA, relaxation of negatively supercoiled DNA and decatenation of kinetoplast DNA. HMGB1 interacts with topo IIalpha and this interaction, like the stimulation of the catalytic activity of the enzyme, requires both HMG-box domains of HMGB1. A mutant of HMGB1, which cannot change DNA topology stimulates DNA decatenation by topo IIalpha indistinguishably from the wild-type protein. Although HMGB1 stimulates ATP hydrolysis by topo IIalpha, the DNA cleavage is much more enhanced. The observed abilities of HMGB1 to interact with topo IIalpha and promote topo IIalpha binding to DNA suggest a mechanism by which HMGB1 stimulates the catalytic activity of the enzyme via enhancement of DNA cleavage.

摘要

DNA拓扑异构酶IIα（topo IIα）是一种必需的核酶，其独特的解连环活性与染色体动态变化的许多方面有关，如有丝分裂期间的染色体复制和分离。在此我们表明，与染色质相关的蛋白质HMGB1（HMG盒蛋白大家族的一员，在DNA复制、转录、重组和DNA修复中可能发挥作用）促进topo IIα介导的环状DNA连环化、负超螺旋DNA松弛以及动质体DNA解连环。HMGB1与topo IIα相互作用，并且这种相互作用，如同对该酶催化活性的刺激一样，需要HMGB1的两个HMG盒结构域。一种不能改变DNA拓扑结构的HMGB1突变体刺激topo IIα进行DNA解连环的作用与野生型蛋白无明显差异。尽管HMGB1刺激topo IIα水解ATP，但DNA切割作用增强得更多。观察到的HMGB1与topo IIα相互作用以及促进topo IIα与DNA结合的能力提示了一种机制，即HMGB1通过增强DNA切割来刺激该酶的催化活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1530/1976466/8a2607e5dcfa/gkm525f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1530/1976466/af17dd415b3c/gkm525f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1530/1976466/981ee5cb7e84/gkm525f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1530/1976466/5cbd21e7fb5a/gkm525f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1530/1976466/0a4ff1f26236/gkm525f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1530/1976466/e9087ccca96c/gkm525f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1530/1976466/1393a2883f3a/gkm525f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1530/1976466/0e5a69fe8ff0/gkm525f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1530/1976466/ccd4fd262b86/gkm525f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1530/1976466/ea2c32b5fc2c/gkm525f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1530/1976466/8a2607e5dcfa/gkm525f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1530/1976466/af17dd415b3c/gkm525f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1530/1976466/981ee5cb7e84/gkm525f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1530/1976466/5cbd21e7fb5a/gkm525f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1530/1976466/0a4ff1f26236/gkm525f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1530/1976466/e9087ccca96c/gkm525f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1530/1976466/1393a2883f3a/gkm525f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1530/1976466/0e5a69fe8ff0/gkm525f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1530/1976466/ccd4fd262b86/gkm525f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1530/1976466/ea2c32b5fc2c/gkm525f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1530/1976466/8a2607e5dcfa/gkm525f10.jpg

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