The role of the Cockayne syndrome protein

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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.