DNA Repair and Chromatin Structure

M.W. Lambert and W.C. Lambert. 1999. DNA repair and chromatin structure in genetic diseases Prog. Nucleic Acid Res. Mol. Biol. 63 257-310. (PubMed)... 

Poly(ADP-Ribosyl)ation, DNA Repair, and Chromatin Structure... 

As described above, histones are much more than passive structural players within chromatin. Dynamic post-translational modifications of these proteins confer specialized chemical proprieties to chromatin of both informational and structural nature with important functional implications. The highly conserved sites for acetylation, methylation, phosphorylation, ADP-ribosylation, and ubiquitination events on histone tails appear to orchestrate functional activities that range from transcriptional activation and repression to DNA repair and recombination. 

Smerdon, M.J. (1991). DNA repair and the role of chromatin structure. Curr. Opin. Cell Biol 3, 422-428. 

McCready SJ, Jackson DA, Cook PR (1982) Attachment of intact superhelical DNA to the nuclear cage during replication and transcription. In Natarajan AT, Obe G, Altmann H (eds) DNA Repair, chromosome alterations and chromatin structure. Elsevier Biomedicine Press, Amsterdam, pp 113-130... 

SURRALLES J, PUERTO S, RAMIREZ MI, CREUS A, MARCOS R, MULLENDERS L H and NATA-RAJAN A T (1998) Links between chromatin structure, DNA repair and chromosome fragility. Mutat Res, 404, 39-44. 

In the nuclei of all eukaryotic cells, DNA is tightly wrapped around an octamer of histone proteins and is compacted into a dense structure known as chromatin. In order to access the genetic information which is required in numerous essential cellular processes including DNA replication, gene expression and DNA repair, chromatin needs to be partially unwound. One important mechanism to regulate chromatin structure and thus to control the access of the genomic DNA is through histone modifications [1-6]. The histone octamer is composed of two copies of H2A, H2B, H3 and H4 core histone proteins. Their tails, that protrude out of the surface of the... 

How does PARP-Fs role as a nucleosome-binding protein and modulator of chromatin structure, which is evident under normal physiological conditions, impact PARP-1-dependent DNA repair, cell death, and inflammatory response pathways, which occur under pathophysiological conditions A number of different scenarios are possible. For example, PARP-l s chromatin-dependent activities may be critical for its function as a DNA repair protein, since the repair of genomic DNA must occur in the context of chromatin. In addition, nucleosome-stimulated autoPARylation may play a role in depleting cellular NAD+ pools in response to cellular stresses. Furthermore, PARP-Fs chromatin-dependent activities may help to regulate the expression of immune and inflammatory response genes. These possibilities will need to be examined in the future. 

---