This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator. Initiation of DNA replication in eukaryotes requires a group of proteins called the Origin Recognition Complex (ORC) which binds to specific sites on DNA called replication origins. Recent work in several labs (some as yet unpublished) has determined the low resolution structures of the ORCs of Yeast and Drosophila, but these are controversial because, although the ORC proteins are homologous, the EM structures are significantly different. Archaea utilise a process more similar to that seen in eukaryotes than bacteria but the organisation is much more simple and hence provides a good model system in helping the understand the eukaryotic process. We are the only lab to be able to assemble an archaeal replication origin in vitro (manuscript under review). We can bind 8 identical ORC1 protein subunits to the 350bp origin DNA (total Mr ~600KDa). Once all eight ORC1 subunits have bound to the origin, the complex then initiates unwinding of an AT-rich region within the origin as a prelude to loading the replicative helicase. We already have crystal structures of the monomeric and dimeric forms of the ORC1 protein alone but we would like to understand the interactions between the subunits when a functional origin is assembled and how this assembly induces unwinding of the replication origin. Although we are trying to crystallise the entire complex, this is an ambitious goal and in the absence of crystals an EM structure would be of enormous help in understanding the assembly process, in particular how the N-terminal AAA+ domains interact with each other within the replication origin complex.
| Bucero, Marta Abril; Bajaj, Chandrajit; Mourrain, Bernard (2016) On the construction of general cubature formula by flat extensions. Linear Algebra Appl 502:104-125 |
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| Jeter, Cameron B; Patel, Saumil S; Morris, Jeffrey S et al. (2015) Oculomotor executive function abnormalities with increased tic severity in Tourette syndrome. J Child Psychol Psychiatry 56:193-202 |
| Zhang, Qin; Cha, Deukhyun; Bajaj, Chandrajit (2015) Quality Partitioned Meshing of Multi-Material Objects. Procedia Eng 124:187-199 |
| Baker, Mariah R; Fan, Guizhen; Serysheva, Irina I (2015) Single-particle cryo-EM of the ryanodine receptor channel in an aqueous environment. Eur J Transl Myol 25:35-48 |
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