Genomic maintenance: the p53 poly(ADP-ribosyl)ation connection.
The integrity of the genome in higher eukaryotes, as well as the modulation of its complex structure and functions, is exquisitely regulated. This genomic regulation occurs as a function of time in a very sophisticated and elaborate biological process called cell cycle progression, resulting in cell division, and is also controlled by a highly coordinated and intricate network of molecular signaling pathways, which in turn orchestrate very specific macromolecular interactions among nuclear proteins and DNA at the biochemical level. Among the latter, a prominent enzymatic cycle that is involved in maintaining the integrity of mammalian chromosomes is covalent protein-poly[adenosine diphosphate (ADP)-ribosyl]ation. The importance of this posttranslational modification is illustrated by the close cooperation between two "guardian angels" of the genome, one constitutive and one inducible protein, namely poly(ADP-ribose) polymerase-1 (PARP-1) and p53, and the integration of these pivotal signaling processes with genomic maintenance.
Department of Biomedical Sciences, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107-2699, USA. ralvarez@hsc.unt.edu
Rafael
R
Alvarez-Gonzalez
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D005057:Eukaryotic Cells / Q000378:metabolism*; D042822:Genomic Instability / Q000502:physiology*; D006801:Humans; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D011064:Poly Adenosine Diphosphate Ribose