FUNCTION OF MITOTIC SUMOYLATION ON GENOMIC INSTABILITY

有丝分裂SUMO化对基因组不稳定性的作用

• 批准号: 7720084
• 负责人: Yoshiaki Azuma
• 金额: $ 2.88万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7720084
• 关键词: Achievement; Address; Binding; Cancer Etiology; Cell division; Cells; Chromosomal Instability; Chromosome Segregation; Chromosome Structures; Chromosomes; Computer Retrieval of Information on Scientific Projects Database; DNA; DNA topoisomerase II alpha; Funding; Genome; Genomic Instability; Genomics; Goals; Grant; Human; Indium; Institution; Mitosis; Mitotic; Mitotic Chromosome; Modification; Molecular; Play; Post-Translational Protein Processing; Proteins; Regulation; Research; Research Personnel; Resources; Role; Source; Therapeutic; Topoisomerase II; Ubiquitin; United States National Institutes of Health; Vertebrate Biology; base; cancer prevention; improved; insight; novel; prevent

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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此，可以在其他清晰的条目中表示。列出的机构是 对于中心，这不一定是调查员的机构。 细胞分裂的基本功能之一是基因组DNA的重复和分离。在细胞分裂有丝分裂期间，复制的基因组DNA均匀分离，以维持完整的基因组信息。与基因组DNA在有丝分裂中的分离特别相关的问题对于理解脊椎动物细胞的基本生物学以及解决因基因组DNA分离而引起的人类癌的分子基础的基本生物学很重要，从而导致基因组不稳定。实现忠实有丝分裂的一个关键要素是蛋白质的修饰。最近的研究表明，小相似的蛋白质修饰，小泛素样修饰剂在有丝分裂过程中在适当的染色体分离中起着至关重要的作用。因此，了解有丝分裂过程中Sumoylation的功能将提供新的信息以防止基因组不稳定，并有望改善预防癌症的治疗剂。为了实现这一目标，我已经将DNA拓扑异构酶II（topoii）确定为主要有丝分裂特异性的sumoylatiod蛋白。为了了解Topoii的Sumoylation的功能，我建议识别潜在的结合伙伴，其与Topoii的关联受到这种修饰的调节，这将调节有丝分裂 - 染色体组织，这将是正常分离染色体所必需的。我已经从有丝分裂染色体中分离出了两种新型的Sumoyyated蛋白质。预计这些新型的Sumoylated蛋白在染色体分离中具有重要作用，并与托托伊的sumoylation一起。通过从该提案中获得的结果，我将深入了解有丝分裂染色体的有丝分裂和调节过程中Sumo修饰的后果。新的信息将提供更好的理解，以防止染色体不稳定性。