Poly(ADP-Ribosyl)ation of Chromosomal Proteins, Epigenetic Regulation and Human Genomic Integrity in Health and Disease

Chapter
First Online:
Part of the Protein Reviews book series (PRON, volume 13)

Abstract

The reproducible and accurate expression of genetic information and the integrity of the human genome, both temporally and topographically, rely heavily on the biochemical ability of nuclear proteins to physically interact with each other, as well as with DNA and RNA, at the molecular level. The strength and specificity of these interactions is primarily determined by the intracellular concentrations of each molecule present. Whereas, the affinity is dictated by the collective primary, secondary, tertiary and quaternary structures of the polypeptides themselves, notwithstanding the intrinsic physicochemical and structural properties of the different types of nucleic acids involved. For the most part, the interactions of DNA with protein molecules occur spontaneously in chromatin because the appropriately folded structures of nuclear proteins are adopted prior to their nucleoplasmic internalization via active and passive transport mechanisms. Once transported into the cell nucleus, most proteins whether, structural in nature, like the histones localized within highly compacted interphase chromatin, or as functional enzymes that modulate chromatin dynamics, such as DNA and RNA polymerases (the catalysts responsible for DNA replication, DNA repair, and transcription) are frequently regulated by unique epigenetic mechanisms of amino acid specific covalent chemical modification, e.g., phosphorylation, acetylation, SUMOylation, nitrosylation, and poly(ADP-ribosyl)ation, just to list a few. Interestingly, while most of these biochemical pathways may be ubiquitous to the cytosolic and plasma membrane compartments, the modification of chromatin proteins via ADP-ribose polymerization, especially when catalyzed by poly(ADP-ribose) polymerases 1 and 2 (PARP-1 and PARP-2), exclusively localizes within the nucleoplasm. Emphasis is placed here to review the current state of the latter, particularly as it pertains to the balance between human health and disease.

Keywords

PARP Inhibitor Genomic Integrity Vide Infra Chromatin Protein Epigenetic Pathway 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Graduate School of Biomedical Sciences, Institute for Cancer ResearchUniversity of North Texas Health Science Center at Fort WorthFort WorthUSA

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