INVESTIGATION INTO THE STRUCTURAL MECHANISM OF ALLOSTERIC MODULATION OF DNA CLEA

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We are investigating the structure of an endonuclease, SgrAI, bound to its target DNA. Endonucleases are important enzymes involved in all aspects of DNA metabolism including replication, recombination, and repair. SgrAI serves to protect its host from invading phage DNA, and oligomerizes on DNA causing sequestration of the activated SgrAI enzyme. Activated SgrAI, caused by oligomerization, cleaves primary site DNA sequences 200 fold faster than the unactived form, and also cleaves more efficiently at secondary site DNA sequences. The secondary sites are not protected in the host DNA, and cleavage by SgrAI would result in genome damage to the host, resulting in strong selective pressure to sequestration of activated SgrAI enzymes. The oligomerization interfaces, and the structures of both activated and unactivated forms of SgrAI, are investigated for their three dimensional structures.