ERCCl is a gene essential for the repair process of UV-induced DNA damage known as Nucleotide Excision Repair (NER). Deficiencies in this DNA repair mechanism have been associated with the skin cancer prone human syndrome Xeroderma Pigmentosum (XP) and also with Cockayne's Syndrome (CS) and Trichothiodystrophy (TTD). The main role of ERCCl is to act as a NER endonuclease but it has also been proposed that it may have a role in recombination. The ERCCl knock out (k/o) mouse model was first described by McWhir et al, in 1993. McWhir and co-workers described ERCCl -deficient mice as being severely runted, dying before weaning at approximately three weeks of age from hepatic failure, having severe aneuploidy and polyploidy in their liver and presenting elevated levels of p53 in this tissue. This k/o model shared no similarities with any of the already known NER deficiency-associated syndromes which led to the theory that a deficiency in the other non-NER ERCCl function(s) may be responsible for the observed differences. The aim of this project was to gain a better understanding of the precise mechanisms behind this atypical phenotype. Indeed, studies carried out on both liver tissue and primary fibroblast material have resulted in the development of a hypothesis for the ERCCl k/o phenotype. No human syndrome has yet been identified as being caused by a defect in ERCCl, so a subsidiary aim of this project was to see if any human condition could be attributed to an ERRC1 deficiency. Taking as a starting point the prematurely aged appearance of the ERCCl k/o mice, a rare human premature ageing syndrome called Hutchinson-Gilford progeria (HGP) was selected as a possible candidate for an ERCCl-related human condition. Primary fibroblasts derived from a HGP patient showed decreased levels of ERCCl protein, but no evidence for mutations in the ERCCl gene was found. However, an impaired p53 response to UV-irradiation was observed. Overall, this work has opened the doors for the study of premature ageing in humans in relationship to NER and p53.