The repair of DNA damage is vital to the health and survival of organisms and their cells. In humans, there exist several disorders that involve the inefficient processing or repair of DNA damage. Cellular sensitivity to DNA-damaging agents is a hallmark of repair-deficient syndromes which are often associated with an increased risk of cancer. In this work, I have investigated the repair of cisplatin-damaged DNA by utilizing host cell reactivation and cellular capacity assays that assess DNA repair using adenovirus (Ad) as a probe. Cisplatin is a widely used chemotherapeutic drug that induces both intrastrand and interstrand crosslinks in DNA. The host cell reactivation (HCR) assay examines the ability) of host cells to repair and hence, replicate cisplatin-damaged Ad DNA. This assay is believed to primarily be a measure of bulk nucleotide excision DNA repair. The cellular capacity assay examines the ability of cisplatin-damaged cells to support the replication of undamaged Ad DNA, and is thought to reflect the repair of the active cellular genes necessary for Ad replication. The repair of cisplatin-damaged DNA was studied in three human genetic syndromes -Roberts syndrome (RS), xeroderma pigmentosum (XP) and Li-Fraumeni syndrome (LFS). Fanconi's anemia (FA) cells were also used as a contml strain. RS is characterized by growth retardation, limb reductions and craniofacial abnormalities. Cell; from a subset of RS patients, termed RS+, are hypersensitive to several DNA-damaging agents, and it has been suggested that this hypersensitivity may result from a deficiency in the DNA repair capacity of these cells. (XP patients are sensitive to ultra violet light and are prone to the development of skin cancers. Cells from these patients are deficient in the nucleotide excision repair (NER) pathway responsible for repair of UV -induced lesions.) Patients with FA have a variety of congenital abnormalities, including a high susceptibility to leukemia. FA cells are sensitive to DNAcrosslinking agents such as mitomycin C (MMC) and cisplatin. Using the HCR and cellular capacity assays, deficiencies in DNA repair were detected in the XP and FA fibroblasts but not in the RS+ fibroblasts when compared to normal strains. The NERdeficient XP cells showed a significant reduction in both HCR of cisplatin-damaged Ad and in their capacity to support Ad replication following cellular cisplatin damage suggesting that cisplatin damage is repaired at least in part by the NER pathway. The normal HCR and capacity response of the RS+ cells compared to the XP cells suggests that the hypersensitivity of RS+ cells to DNA damage is not due to a deficiency in NER. The FA cells had normal HCR of cisplatin-damaged Ad but were significantly reduced in their capacity to support Ad replication following cisplatin treatment which was attributed to a defici,~ncy in the repair of DNA interstrand crosslinks. RS+ cells were not reduced in their capc.city to support Ad DNA replication, suggesting that the RS+ cellular hypersensitivity doe; not result from a deficiency in interstrand crosslink repair as seen with FA cells. LFS is a cancer prone syndrome that involves mutations in the p53 tumour suppressor gene. It was found that HCR of cisplatin-damaged Ad was normal in both p53-heterozygous and -hemizygous LFS cells, whereas the NER-deficient XP cells had significantly reduced HCR. The capacity of cisplatin-damaged, p53-heterozygous LFS fibroblasts was significantly reduced compared to normal cells. This suggests that although the LFS fibroblasts appear to have normal bulk NER, as shown by HCR, they appear to be deficier in the repair of the actively transcribed cellular genes necessary for viral replication. These results suggest a role for p53 in the repair of cisplatin damage of active genes. / Thesis / Master of Science (MS)