The proteins CSA and CSB are mutant in Cockayne syndrome while the XPB and XPD proteins are defective in patients with Xeroderma pigmentosum.
In Cockayne syndrome, the patients develop variety of symptoms associated with premature aging whereas in XP patients develop early cancers. In Cockayne syndrome, the defective proteins cannot recognize RNA (ribonucleic acid) polymerase complexes stalled by DNA (deoxyribonucleic acid) damage. A consequence of this defect is that the cell is more likely to activate the apoptosis suicide pathway. In a healthy person cell death is often preferable to the propagation of a cell that has sustained DNA damage. According to this theory, the cell-death pathway would be activated more frequently in a Cockayne syndrome patient leading to premature aging symptoms.
The defects observed in Cockayne syndrome may be the result of both apoptosis and a failure to repair lesions.
XP patients can recognize stalled transcription complexes as they have normal CSA and CSB proteins and prevent cell death when transcription is restarted. But they cannot repair the original damage because of mutations in one of their XP proteins. Hence, mutations will accumulate in the cells of patients with XP and the presence of mutations caused by mutagens or the failure of repair pathways increases the risk of developing many types of cancer.
XP defects may result primarily from a failure to repair DNA.