The CSB protein (Cockayne syndrome complementation group B) plays an important role in transcription, DNA repair and the maintenance of chromosome structure. Mutations in CSB have been found to be associated with a variety type of human cancers including lung, breast, colon and pancreatic cancers. However their role in tumorigenesis has not been characterized. We propose that cancer-associated CSB mutations affect chromosome stability and DNA repair and thereby promote cancer. The objective of the proposed research is aimed at characterizing the effect of cancer-associated CSB mutations on the maintenance of chromosome stability as well as on the repair of ultraviolet-induced DNA damage and oxidative damage. The proposed studies are expected to determine the role of cancer-associated CSB mutations in tumorigenesis as well as to help the design of the effective cancer treatment.