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Date of Award
Nutrition and Food Science
Diane C. Cabelof
Down syndrome (DS) is a chromosomal condition characterized by accelerated aging that has yet to be directly linked to a DNA repair defect. Reduced PolB and unrepaired damage from oxidative stress observed in DS, point toward defective base excision repair (BER). In this study, we report that low PolB transcript correlates with increased markers of senescence. The gene dosage effect of Trisomy 21 is likely the source for PolB downregulation. We show that the HSA21-localized miR-155 overexpression correlates with a decrease in Creb1 and PolB, thus establishing a putative regulatory pathway. Data from the DS mouse model, Ts65Dn, reveal low incidence of solid tumors consistent with clinical observations. Our findings establish Polβ as a causative factor of senescence, suggesting that base excision repair is one of the processes driving aging in Down syndrome.
Ahmed, Aqila Ahmed, "Investigating The Role Of Dna Polymerase Beta In The Aging Phenotype Of Down Syndrome" (2016). Wayne State University Dissertations. 1617.