title: Human cancer and DNA repair-deficient diseases.
abstract: Cancer development requires the accumulation of numerous genetic changes which are usually believed to occur through the presence of unrepaired DNA lesions. Exogenous or endogenous DNA-damaging agents can lead to mutations in the absence of efficient error-free repair, via replication of DNA damage. Several DNA repair pathways are present in living cells and well conserved from bacteria to human cells. Apart from mismatch repair, photolyases, base excision, and postreplication repair, the nucleotide excision repair (NER), the most versatile of these DNA repair systems, recognizes and eliminates a wide variety of DNA lesions and particularly those induced by ultraviolet (UV) light. The phenotypic consequences of an NER defect in humans are apparent in rare but dramatic diseases characterized by hypersensitivity to UV and a striking clinical and genetic heterogeneity. The xeroderma pigmentosum syndrome (XP), the Cockayne's syndrome (CS), and the photosensitive form of trichothiodystrophy (TTD) are three of these clinically distinct human disorders inherited as an autosomal recessive trait. Persistence of unrepaired DNA damage produced by exposure to UV light is associated, in the XP syndrome, with an extremely high level of skin tumors in sun-exposed sites. But the direct link of defective DNA repair to cancer seems to be complex, since, in contrast to patients with XP, those with TTD or CS do not have an increased frequency of skin cancers. The understanding of the absence of skin tumors in TTD and CS patients may offer a way to better protect normal individuals from the most rapidly increasing cancer: skin cancer.
authors.affiliation: Laboratory of Molecular Genetics, UPR 42, CNRS-IFC1, Villejuif, France.
authors.forename: A
authors.initials: A
authors.lastname: Sarasin
authors.forename: A
authors.initials: A
authors.lastname: Stary
mesh_terms: D003057:Cockayne Syndrome / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics; D011088:DNA Ligases / Q000172:deficiency / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D005199:Fanconi Anemia / Q000235:genetics*; D006201:Hair Diseases / Q000235:genetics*; D006801:Humans; D014983:Xeroderma Pigmentosum / Q000235:genetics*
chemical_list: D011088:DNA Ligases