High mobility group chromosomal protein 1 binds to the adeno-associated virus replication protein (Rep) and promotes Rep-mediated site-specific cleavage of DNA, ATPase activity and transcriptional repression

被引:75
作者
Costello, E
Saudan, P
Winocour, E
Pizer, L
Beard, P
机构
[1] SWISS INST EXPT CANC RES,CH-1066 EPALINGES,SWITZERLAND
[2] WEIZMANN INST SCI,DEPT MOL GENET,IL-76100 REHOVOT,ISRAEL
[3] UNIV COLORADO,HLTH SCI CTR,DEPT MICROBIOL,DENVER,CO 80262
关键词
AAV; ATPase; DNA endonuclease; HMG1; transcription;
D O I
10.1093/emboj/16.19.5943
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
High mobility group protein 1 (HMG1) is an abundant non-histone chromosomal protein which plays a role in several nuclear events involving DNA. Here we demonstrate that HMG1 physically interacts with the human adeno-associated virus (AAV) Rep protein, HMG1 promotes the formation of Rep-DNA complexes and stimulates the activity of Rep in site-and strand-specific cleavage of DNA and the hydrolysis of ATP, functions required for viral gene regulation, replication and site-specific integration of viral DNA into human chromosome 19, We show that HMG1 enhances Rep-mediated repression of the AAV p5 promoter in transfected cells, suggesting that HMG1 and Rep also interact irt vivo, HMG1, Rep and DNA can be immunoprecipitated as a ternary complex. Kinetic studies indicate that complexes of Rep with DNA have similar stabilities in the presence and absence of HMG1. These results suggest that the effect of HMG1 on Rep binding is exerted at the step of complex formation and thereby may reflect an activity of HMG1 in promoting the assembly of complex cellular nucleoprotein structures.
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页码:5943 / 5954
页数:12
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