Changes in nuclear protein acetylation in u.v.-damaged human cells

• Published in: Carcinogenesis (New York) 1986-07, Vol.7 (7), p.1087-1094
• Main Authors: Ramanathan, Brinda, Smerdon, Michael J.
• Format: Article
• Language: English
• Subjects: Acetates - metabolism; Acetic Acid; Acetylation; Biological and medical sciences; Cells, Cultured; Chromosomal Proteins, Non-Histone - metabolism; Dose-Response Relationship, Radiation; Electrophoresis, Polyacrylamide Gel; Fibroblasts - radiation effects; Fundamental and applied biological sciences. Psychology; Humans; Lysine - metabolism; Molecular and cellular biology; Molecular genetics; Molecular Weight; Mutagenesis. Repair; Nucleoproteins - metabolism; Time Factors; Ultraviolet Rays
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/7.7.1087

We have investigated the levels of nuclear protein acetylation in u.v.-irradiated human fibroblasts. Initially, we measured the levels of acetylation in total acid-soluble nuclear proteins and observed two distinct differences between the irradiated and unirradiated (control) cells. Immediately after irradiation, there is a ‘wave’ of protein hyperacetylation (i.e. a total acetylation level greater than that of unirradiated cells) that lasts for 2–6 h depending on the experimental conditions. This hyperacetylation phase is then followed by a hypoacetylation phase, lasting for many hours, and the total level of acetylation does not return to that of control cells until 24–72 h after u.v. damage. Both the magnitude and duration of each phase is dependent on the dose of u.v. light used. The wave of hyperacetylation is more pronounced at low u.v. doses (i.e. 8 J/m2). Furthermore, the duration of each phase is prolonged when cells are exposed to 2 mM hydroxyurea, an agent which retards the rate of excision repair at u.v.-damaged sites. Examination of the acetylation levels of the individual nuclear proteins indicated that acetylation of the core histories follows the same pattern observed for the total acid-soluble protein fractions. Furthermore, these were the only major proteins in the total acid-soluble fraction observed to undergo the early, rapid hyperacetylation immediately following u.v. damage. Acetylation of histone HI was negligible in both damaged and control cells, while three prominent non-histone proteins were acetylated only after long labeling times (>4 h) in each case, gradually becoming hyperacetylated in the u.v.-damaged cells. These results raise the possibility that a causal relationship exists between nuclear protein acetylation and nucleotide excision repair of DNA in human cells.