Date of Award

1-1-2012

Language

English

Document Type

Master's Thesis

Degree Name

Master of Science (MS)

College/School/Department

Department of Chemistry

Content Description

1 online resource (ii, 36 pages) : illustrations (some color)

Dissertation/Thesis Chair

John Welch

Keywords

Sirtuins

Subject Categories

Biochemistry

Abstract

ABSTRACT: Sirtuins, possessing either histone deacetylase or mono-ribosyltransferase activity, regulate important biological pathways in bacteria, archaea and eukaryotes. The term Sir2 comes from the yeast 'silent mating-type information regulation 2' gene, a gene directing cellular regulation in yeast. Sirtuins have been implicated in aging, regulation of transcription, apoptosis and stress resistance, in addition to energy efficiency and metabolism. In mammals, a variety of sirtuin family members are genetically encoded to include sirtuins 1-7 (SIRT1-SIRT7). SIRT6 is a human sirtuin of interest in a variety of research areas, influencing the genomic instability, metabolic defects and degenerative pathologies associated with aging. Until recently, SIRT6 was an orphan enzyme whose catalytic activity and substrates were unclear. However, new mechanistic insights have been derived from the discovery of the highly substrate-specific histone deacetylase activity of SIRT6 to promote proper chromatin function in several physiologic contexts; that include telomere and genome stabilization, gene expression and DNA repair. By maintaining both the integrity and the expression of the mammalian genome, SIRT6 demonstrates several actions intimately related to Sir2 function. In this article the action of SIRT6 is described, emphasizing the various cellular roles and the relation of those functions to human biology and disease.

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