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Damage specific DNA binding protein (DDB) functions in nucleotide-excision repair. Its defective activity causes the repair defect in the patients with xeroderma pigmentosum complementation group E (XPE). To test whether the DNA-repair defect in the subset of XPE patients that lack DNA damage-binding activity is caused by a defect in DDB, purified human DDB protein was injected into XPE cells. The injected DDB protein stimulated DNA repair to normal levels in those strains that lacked the DDB activity but did not stimulate repair in cells from XPE patients that contained the activity. These results provided direct evidence that defective DDB activity causes the repair defect in a subset of XPE patients and establishes a role for this activity in nucleotide excision repair in vivo. It remains for mutation analysis to demonstrate whether the defect in XPE patients is in the DDB1 gene or the DDB2 gene.
