Carolina Quayle
From DNA Repair Lab
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Research abstract
DNA lesions, if not corrected, may result in mutations, cell death and cancer. Ultraviolet (UV) radiation is the most carcinogenic exogenic factor in our environment nowadays, causing mostly cyclobutane pirimidine dimers (CPDs) and 6-4 pirimidine-pirimidone photoproducts (6-4PPs). Photolyases are enzimes capable of reverting these lesions in a specific and direct way, using visible light as source of energy. Placental mammals lack these enzymes and dispose only of nucleotide excision repair (NER) pathway to remove double-helix distorting lesions. Despite the extensive research that has been done, in vitro and in vivo, the role of each lesion in apoptosis, tumorigenesis, edema and other effects induced by UV light is still unclear. Based in the results obtained with cells profficient and defficient in different repair genes and in mice profficient in DNA repair, we suggest that in individuals proficient in all DNA repair genes, CPDs lesions are responsible for cancer induction since its removal its slower. Thus, in NER defficient individuals, 6-4PP lesions must be responsible for the vast majority of the UV effect since it is a more helix-distorcing lesion. Since all in vivo experiments have used DNA repair proficent mice, we suggest the development of experiments using mice defficient in the NER pathway. Nockdown mice in the XPA and XPC genes of the NER pathway present a similar phenotype to xeroderma pigmentosum (XP) patients, including hipersensibility to UV light with increased risk of cancer. The goal of this work is to analyse the role of CPD and 6-4PP lesions in vivo, using XP mice transduced with specific photolyase in an adenoviral vector, treated with UVB radiation. Preliminary data suggests shows protection in both groups.
Finantial support
FAPESP
Selected publications
Mercuri LP, Carvalho LV, Lima FA, Quayle C, Fantini MC, Tanaka GS, Cabrera WH, Furtado MF, Tambourgi DV, Matos Jdo R, Jaroniec M, Sant'Anna OA. Ordered mesoporous silica SBA-15: a new effective adjuvant to induce antibody response. Small, 2(2):254-6, 2006.