POLY (ADP-RIBOSYL)ATION OF VARIANT HISTONES AND POSSIBLE IMPLICATIONS IN CARCINOGENESIS
Poly(ADP-ribose) is a third species of nucleic acids. The rapid synthesis and degradation of poly(ADP-ribose) is a dynamic nuclear process that seems to be involved in carcinogenesis via its implication in repair, replication, gene expression, recombination and chromatin remodeling in development. In the present study, the ADP-ribosylated species of histones synthesized in human erythroid K562 cell nuclei were examined by high-resolution two-dimensional polyacrylamide gel electrophoresis. Modification of core histone variants appears to be highly specific. Variants of histone H3 are modified with one or more than five ADP-ribosyl groups, whereas the concentrations of di-, tri- and tetra(ADP-ribosyl)ated H3 is extremely low. This is in contrast to the presence of a continuous ladder of mono- to poly(ADP-ribosyl)ated species for the variants of H2B, H2A, H1 and H4. The order of poly(ADP-ribosyl)ation of core histones in isolated nuclei is H2B > H2A.X > H3.2,3 approximately H4 > H2A.Z approximately H3. 1. A model is proposed to explain how mono- and oligo(ADP-ribosyl)ated core histones containing 1 - 7 ADP-ribosyl groups might unfold higher-order chromatin structures and open individual nucleosomes into transcriptionally poised structures. The relevance of these studies to molecular carcinogenesis are discussed.
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Document Type: Research Article
Publication date: January 1, 1993
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- The International Journal of Oncology provides an international forum for the publication of the latest, cutting-edge research in the broad area of oncology and cancer treatment. The journal accepts original high quality works and reviews on all aspects of oncology research including carcinogenesis, metastasis, epidemiology, chemotherapy and viral oncology. Through fair and efficient peer review, the journal is dedicated to publishing top tier research in the field, offering authors rapid publication as well as high standards of copy-editing and production. The International Journal of Oncology is published on a monthly basis in both print and early online.
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