IMPLICATIONS OF DNA REPLICATION FORK PROTEINS FOR CANCER

DNA 复制叉蛋白对癌症的影响

• 批准号: 8360071
• 负责人: Karen H. Almeida
• 金额: $ 18.65万
• 依托单位: UNIVERSITY OF RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360071
• 关键词: Affect; BLM gene; Behavioral Research; Biochemical; Biochemistry; Biomedical Research; Bloom Syndrome; Cells; Chromosome Segregation; DNA Repair; DNA biosynthesis; DNA replication fork; Deletion Mutation; Development; Discipline; Disease; Drosophila genus; Family member; Funding; Genetic; Genome; Genome Stability; Genomic Instability; Grant; Incidence; Lead; Malignant Neoplasms; Molecular Biology; Molecular Genetics; Mutation; National Center for Research Resources; Pathway interactions; Principal Investigator; Procedures; Proteins; RecQ protein; Regulation; Research; Research Infrastructure; Resources; Role; Source; United States National Institutes of Health; cancer cell; cohesion; cost; helicase; member; protein function; repaired; research study

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. A unifying feature of cancer cells is an unstable genome. To achieve normal development, a cell must accurately coordinate pathways affecting DNA replication, chromosome segregation and DNA damage repair. Mishaps in any of these procedures can lead to instability in the genome and ultimately to a higher incidence of cancer development. Therefore, these mechanisms must be highly orchestrated and rigorously regulated. Accumulating evidence demonstrates that there are particular molecules that bridge these pathways to insure coordinate regulation. Many of these molecules have overlapping functions for DNA replication and repair and chromosome segregation. This study focuses on members of the RecQ helicase superfamily of proteins that function at replication forks and have roles in DNA repair and chromosome segregation. Bloom Syndrome is a recessive disorder resulting from mutation in the Bloom Syndrome gene (BLM) and characterized by increased genomic instability and enhanced onset of cancer. The physical and functional biochemical studies undertaken will identify and refine the sub-domains of Blm responsible for partnerships with known DNA repair and replication proteins to clarify the exact role of Blm in genomic stability. Furthermore, Chl1p is a newly identified RecQ family member in Drosophila and is implicated in bridging DNA replication and chromosomal cohesion. This study will identify the function of Chl1p in Drosophila by genetic deletion and mutations in Chl1p. Overall, the experiments span the disciplines of biochemistry, molecular biology and genetics to investigate the RecQ protein partnerships responsible for the accurate progression through DNA replication, repair and chromosome segregation.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 癌细胞的统一特征是不稳定的基因组。为了达到正常发育，细胞必须准确地坐定影响DNA复制，染色体分离和DNA损伤修复的途径。这些程序中的任何一个都可能导致基因组的不稳定，并最终导致癌症发展的发病率更高。因此，这些机制必须高度精心策划和严格调节。积累的证据表明，有一些特定的分子可以桥接这些途径以确保坐标调节。这些分子中的许多具有重叠的DNA复制和修复和染色体分离的功能。这项研究的重点是蛋白质的RECQ解旋酶超家族的成员，这些蛋白质在复制叉上起作用，并在DNA修复和染色体分离中起作用。 Bloom综合征是由Bloom综合征基因（BLM）突变引起的隐性疾病，其特征是基因组不稳定性增加和癌症的发作增强。进行的物理和功能性生化研究将识别和完善负责具有已知DNA修复和复制蛋白伙伴关系的BLM的子域，以阐明BLM在基因组稳定性中的确切作用。此外，CHL1P是果蝇中新鉴定的RECQ家族成员，与桥接DNA复制和染色体凝聚有关。这项研究将通过遗传缺失和CHL1P突变确定CHL1P在果蝇中的功能。总体而言，实验涵盖了生物化学，分子生物学和遗传学的学科，以研究RECQ蛋白质伙伴关系通过DNA复制，修复和染色体隔离来准确进展的RECQ蛋白伙伴关系。