Gene Expression Profiling of Xeroderma Pigmentosum

Using gene expression analysis we have identified similarities and differences after UV light exposure between the complementation groups XP-A, XP-C, XP-D, XP-E, XP-F, XP-G and an unaffected control. The results reveal that there is a graded change in gene expression patterns between the mildest, most similar to the control response (XP-E) and the severest form (XP-A) of the disease, with the exception of XP-D. Distinct differences between the complementation groups with neurological symptoms (XP-A, XP-D and XP-G) and without (XP-C, XP-E and XP-F) were also identified. Therefore, this analysis has revealed distinct gene expression profiles for the XP complementation groups and the first step towards understanding the neurological symptoms of XP.The structural integrity of chromosomal DNA is of paramount importance for the survival of a cell, an organism and indeed an entire species [1]. The faithful passage of this nucleotide blueprint requires its stable transition between successive cellular generations [2]. Both replicating and non-replicating DNA are vulnerable to various forms of errors and lesions that constitute or lead to gene mutations [3]. To counteract the effects of mutagenic and carcinogenic agents all organisms are equipped with a sophisticated network of DNA repair systems that are essential for genetic stability [4]. The identification of several cancer syndromes in humans where the causative factor is a genetic mutation in a component of one or more of the DNA repair systems has highlighted the importance of maintaining DNA integrity.Exogenous DNA mutagenesis is a consequence of external agents impacting on the integrity of cellular DNA. These agents can be divided into three classes: ultraviolet (UV) irradiation, ionising irradiation and alkylating agents. DNA repair is an important molecular defence system in which mutations caused by these agents in actively transcribed genes are preferentially repaired. All damaged DNA is repaired before DNA rep