THE LOSS OF GENOMIC URACIL HOMEOSTASIS AND AID-DEPENDENTACCUMULATION OF DNA DAMAGE IN B CELL LYMPHOMASbySOPHIA SHALHOUTMay 2015Advisor: Dr. Ashok S. BhagwatMajor: Chemistry (Biochemistry)Degree: Doctor of PhilosophyActivation-induced deaminase (AID) is a sequence-selective DNA cytosinedeaminase that introduces uracils in immunoglobulin genes. This DNA mut...

Infrared absorption spectra, in the vapour phase, have been recorded in the regions of NH, OH and carbonyl stretching frequencies, for a series of 1-substituted uracils and 9-substituted adenine and hypoxanthine, formal analogues of the natural nucleosides of uracil, adenine and hypoxanthine found in DNA and/or RNA. A number of related analogues was also examined, including the N-methyl derivat...

The [2 + 2] photochemical cycloadditions (the Paternò-Büchi reaction) of 5- or/and 6-methyl substituted uracil derivatives with 4,4'-disubstituted benzophenones generate two series of regioisomeric oxetanes, 3 and 4. The regioselectivity (3/4) and the photochemical efficiency are strongly dependent on methyl substituent(s) at the C5-C6 double bond of the uracils. The more the methyl groups at t...

Ig gene conversion is most likely initiated by activation-induced cytidine deaminase-mediated cytosine deamination. If the resulting uracils need to be further processed by uracil DNA glycosylase (UNG), UNG inactivation should block gene conversion and induce transition mutations. In this study, we report that this is indeed the phenotype in the B cell line DT40. Ig gene conversion is almost co...

A variety of structural analogues of purines and pyrimidines are known to affect the growth of viruses, bacteria and other micro-organisms, plants and animals. Some of these may exert their action through being incorporated into nucleic acids in place of the natural purine or pyrimidine. Such examples are: 8-azaguanine, a structural analogue of guanine, which has been shown to replace guanine i...

8-Aminoquinoline (8AQ) derivatives have been reported to have antimalarial, anticancer, and antioxidant activities. This study investigated the potency of 8AQ-5-substituted (iodo and nitro) uracils metal (Mn, Cu, Ni) complexes (1-6) as antimalarial and antimicrobial agents. Interestingly, all of these metal complexes (1-6) showed fair antimalarial activities. Moreover, Cu complexes 2 (8AQ-Cu-5I...