The role of the Cockayne syndrome protein

科凯恩综合征蛋白的作用

• 批准号: 10471687
• 负责人: Vilhelm A Bohr
• 金额: $ 125.67万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10471687
• 关键词: Aging; Base Excision Repairs; Biological Models; Cachexia; Cockayne Syndrome; DNA Damage; DNA Repair; DNA Repair Pathway; Disease; Excision; Genetic Transcription; Genome Stability; Lesion; Metabolism; Mitochondrial DNA; Mutation; Nerve Degeneration; Nuclear; Nucleotides; Oxidative Stress; Pathway interactions; Premature aging syndrome; Proteins; Reporting; Role; oxidative DNA damage; protein function; repaired; response

Cockayne syndrome (CS) is a devastating autosomal recessive disease characterized by neurodegeneration, cachexia, and is a segmental premature aging disorder. Mutations in CSA and CSB predominantly cause CS. There are deficiencies in the repair of oxidative DNA damage in both nuclear and mitochondrial DNA, and this may contribute to CS disease features. Previously, we demonstrated that the CSB protein interacts with PARP1, a protein involved in the early steps of DNA damage repair, and that these two proteins cooperate in the cellular responses to oxidative stress. More recently, CSBs physical and functional interactions with LEO1 at transcription-blocking lesions were reported. This provides new understanding about the role of the CS protein in transcription. CS proteins function in multiple repair pathways and their diverse roles have implications for genome stability and premature aging features. We are continuing to investigate the role of CS proteins in DNA damage and repair.

Cockayne综合征(CS)是一种以神经变性、恶病质为特征的常染色体隐性遗传病，是一种节段性早衰疾病。CsA和CSB的突变主要导致CS。核DNA和线粒体DNA氧化损伤的修复都存在缺陷，这可能是CS疾病的特征之一。在此之前，我们证明了CSB蛋白与PARP1蛋白相互作用，PARP1蛋白参与DNA损伤修复的早期步骤，这两种蛋白在细胞对氧化应激的反应中相互作用。 最近，CSB与LEO1在转录阻断损伤中的物理和功能相互作用被报道。这对CS蛋白在转录中的作用提供了新的理解。CS蛋白在多种修复途径中发挥作用，它们的不同作用对基因组稳定性和早衰特征具有重要意义。我们正在继续研究CS蛋白在DNA损伤和修复中的作用。