HIGH-MOBILITY GROUP CHROMOSOMAL PROTEIN-1 BINDS TO THE ADENOASSOCIATED VIRUS-REPLICATION PROTEIN (REP) AND PROMOTES REP-MEDIATED SITE-SPECIFIC CLEAVAGE OF DNA, ATPASE ACTIVITY AND TRANSCRIPTIONAL REPRESSION

High mobility group protein 1 (HMG1) is an abundant non-histone chromo somal protein which plays a role in several nuclear events involving D NA. 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 st rand-specific cleavage of DNA and the hydrolysis of ATP, functions req uired for viral gene regulation, replication and site-specific integra tion 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 indic ate that complexes of Rep with DNA have similar stabilities in the pre sence and absence of HMG1. These results suggest that the effect of HM G1 on Rep binding is exerted at the step of complex formation and ther eby may reflect an activity of HMG1 in promoting the assembly of compl ex cellular nucleoprotein structures.