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Title: N-Butyrate alters chromatin accessibility to DNA repair enzymes

Abstract

Current evidence suggests that the complex nature of mammalian chromatin can result in the concealment of DNA damage from repair enzymes and their co-factors. Recently it has been proposed that the acetylation of histone proteins in chromatin may provide a surveillance system whereby damaged regions of DNA become exposed due to changes in chromatin accessibility. This hypothesis has been tested by: (i) using n-butyrate to induce hyperacetylation in human adenocarcinoma (HT29) cells; (ii) monitoring the enzymatic accessibility of chromatin in permeabilised cells; (iii) measuring u.v. repair-associated nicking of DNA in intact cells and (iv) determining the effects of n-butyrate on cellular sensitivity to DNA damaging agents. The results indicate that the accessibility of chromatin to Micrococcus luteus u.v. endonuclease is enhanced by greater than 2-fold in n-butyrate-treated cells and that there is a corresponding increase in u.v. repair incision rates in intact cells exposed to the drug. Non-toxic levels of n-butyrate induce a block to G1 phase transit and there is a significant growth delay on removal of the drug. Resistance of HT29 cells to u.v.-radiation and adriamycin is enhanced in n-butyrate-treated cells whereas X-ray sensitivity is increased. Although changes in the responses of cells to DNA damaging agents mustmore » be considered in relation to the effects of n-butyrate on growth rate and cell-cycle distribution, the results are not inconsistent with the proposal that increased enzymatic-accessibility/repair is biologically favourable for the resistance of cells to u.v.-radiation damage. Overall the results support the suggested operation of a histone acetylation-based chromatin surveillance system in human cells.« less

Authors:
Publication Date:
Research Org.:
MRC Clinical Oncology and Radiotherapeutics Unit, Cambridge, England
OSTI Identifier:
5738815
Resource Type:
Journal Article
Journal Name:
Carcinogenesis; (United States)
Additional Journal Information:
Journal Volume: 3
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; BUTYRIC ACID; RADIOSENSITIVITY EFFECTS; CELL CYCLE; CHROMATIN; DNA REPAIR; DOXORUBICIN; ESTERS; PYRIMIDINE DIMERS; TUMOR CELLS; ULTRAVIOLET RADIATION; X RADIATION; ANIMAL CELLS; ANTI-INFECTIVE AGENTS; ANTIBIOTICS; ANTINEOPLASTIC DRUGS; BIOLOGICAL RECOVERY; BIOLOGICAL REPAIR; CARBOXYLIC ACIDS; DRUGS; ELECTROMAGNETIC RADIATION; IONIZING RADIATIONS; MONOCARBOXYLIC ACIDS; ORGANIC ACIDS; ORGANIC COMPOUNDS; RADIATIONS; RECOVERY; REPAIR; 560121* - Radiation Effects on Cells- External Source- (-1987)

Citation Formats

Smith, P J. N-Butyrate alters chromatin accessibility to DNA repair enzymes. United States: N. p., 1986. Web. doi:10.1093/carcin/7.3.423.
Smith, P J. N-Butyrate alters chromatin accessibility to DNA repair enzymes. United States. https://doi.org/10.1093/carcin/7.3.423
Smith, P J. 1986. "N-Butyrate alters chromatin accessibility to DNA repair enzymes". United States. https://doi.org/10.1093/carcin/7.3.423.
@article{osti_5738815,
title = {N-Butyrate alters chromatin accessibility to DNA repair enzymes},
author = {Smith, P J},
abstractNote = {Current evidence suggests that the complex nature of mammalian chromatin can result in the concealment of DNA damage from repair enzymes and their co-factors. Recently it has been proposed that the acetylation of histone proteins in chromatin may provide a surveillance system whereby damaged regions of DNA become exposed due to changes in chromatin accessibility. This hypothesis has been tested by: (i) using n-butyrate to induce hyperacetylation in human adenocarcinoma (HT29) cells; (ii) monitoring the enzymatic accessibility of chromatin in permeabilised cells; (iii) measuring u.v. repair-associated nicking of DNA in intact cells and (iv) determining the effects of n-butyrate on cellular sensitivity to DNA damaging agents. The results indicate that the accessibility of chromatin to Micrococcus luteus u.v. endonuclease is enhanced by greater than 2-fold in n-butyrate-treated cells and that there is a corresponding increase in u.v. repair incision rates in intact cells exposed to the drug. Non-toxic levels of n-butyrate induce a block to G1 phase transit and there is a significant growth delay on removal of the drug. Resistance of HT29 cells to u.v.-radiation and adriamycin is enhanced in n-butyrate-treated cells whereas X-ray sensitivity is increased. Although changes in the responses of cells to DNA damaging agents must be considered in relation to the effects of n-butyrate on growth rate and cell-cycle distribution, the results are not inconsistent with the proposal that increased enzymatic-accessibility/repair is biologically favourable for the resistance of cells to u.v.-radiation damage. Overall the results support the suggested operation of a histone acetylation-based chromatin surveillance system in human cells.},
doi = {10.1093/carcin/7.3.423},
url = {https://www.osti.gov/biblio/5738815}, journal = {Carcinogenesis; (United States)},
number = ,
volume = 3,
place = {United States},
year = {Sat Mar 01 00:00:00 EST 1986},
month = {Sat Mar 01 00:00:00 EST 1986}
}