The role of the Cockayne syndrome protein

柯凯因综合征（CS）是一种毁灭性的常染色体隐性遗传病，其特征为神经变性、恶病质，是一种节段性早衰疾病。CSA和CSB突变是导致CS的主要原因。细胞核和线粒体DNA的氧化DNA损伤修复都存在缺陷，这可能是导致CS疾病特征的原因之一。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，并且这两种蛋白在细胞对氧化应激的反应中合作。PARP1在DNA损伤后分解NAD，我们已经证明在CS小鼠样本中NAD I的分解速度较慢。此外，我们已经证明补充烟酰胺核苷可以减轻CS的一些特征。我们正在继续研究CSA和CSB蛋白在与CS相关的多系统疾病中的作用。

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. PARP1 catabolizes NAD following DNA damage and we have shown that NAD I slower in CS mice samples. Further, we have shown that supplementation with nicotinamide riboside can mitigate some features of CS. We are continuing to investigate the role of CSA and CSB proteins in the multisystemic diseases associated with CS.