Browsing by Author "Demorest, Zachary Lee"

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    Post-translational regulation of mammalian DNA cytidine deaminases.
    (2012-06) Demorest, Zachary Lee
    Our immune system is faced with the challenge of neutralizing the daily bombardment of invading pathogens. This requires two major response mechanisms in order to achieve this task. The innate immune system acts quickly in response to nonspecific bacterial, viral and nucleic acid based antigens to prevent the onset of disease. In contrast, the adaptive immune system functions slowly but has the added advantage of providing memory and long-term immunity to specific pathogens. Two members of the AID/APOBEC family of cytidine deaminases, APOBEC3G (A3G) and activationinduced deaminase (AID), are critical components of the innate and adaptive immune responses. A3G is a potent inhibitor of Human Immunodeficiency Virus type-1 (HIV-1) as well as a number of other endogenous replicative elements that threaten our genomic integrity. This is accomplished by actively mutating cytosines to uracil in the viral genome during replication. These mutations render the virus non-functional and therefore incapable of spreading infection. AID is necessary for our bodies to generate a diverse antibody repertoire. This is achieved through the initiation of class-switch recombination and somatic hypermutation, processes that allow developing B-cells to generate antibodies of varying isotype with a high specificity for a given antigen. Both of these enzymes, AID and A3G, are DNA mutating enzymes with the potential to wreak havoc on our genome and contribute to cancer. The regulation of these enzymes is multifaceted, involving differential transcription, miRNAs, subcellular localization, interactions with regulatory proteins, and post-translational modifications.