FUNCTION OF MITOTIC SUMOYLATION ON GENOMIC INSTABILITY

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. One of the fundamental functions of cell division is the duplication and separation of genomic DNA. Replicated genome DNA is evenly segregated during mitosis of cell division to maintain complete genomic information. Questions specifically related to separation of genomic DNA in mitosis are important both in understanding the fundamental biology of vertebrate cells and in addressing the molecular basis of human cancers caused by mis-regulation of genomic DNA separation resulting in genomic instability. One key element in achievement of faithful mitosis is modifications of proteins. Recent studies indicate that the protein modification by SUMO, Small Ubiquitin-like MOdifier, plays a crucial role in proper chromosomal separation during mitosis. Therefore, understanding the function of SUMOylation during mitosis will provide novel information to prevent genomic instability and is expected to improve therapeutics for cancer prevention. Toward that goal, I have identified DNA topoisomerase II (TopoII) as a major mitotic-specific SUMOylatiod protein. To understand the function of SUMOylation of TopoII, I propose to identify potential binding partners whose association to TopoII is regulated by this modification, which will regulate mitotic-chromosomal organization that will be required for normal separation of chromosomes. I have isolated two novel SUMOylated proteins from mitotic chromosomes. These novel SUMOylated proteins are expected to have an important role in chromosome segregation together with SUMOylation of TopoII. Through the results obtained from this proposal, I will gain insight into the consequences of SUMO modification during mitosis and regulation of mitotic chromosomes. The novel information will provide better understanding to prevent chromosomal instability.