Poly(ADP-ribosyl)ation of Histone H1 Correlates with Internucleosomal DNA Fragmentation during Apoptosis (*)
- Yoo Sik Yoon(1),
- Jin Woo Kim(1),
- Ke Won Kang(1),
- Young Sang Kim(2),
- Kyung Hee Choi(3) and
- Cheol O Joe(1)(§)
- From the (1)Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejon, 305-701, South Korea, the
- (2)Department of Biochemistry, Chungnam National University, Taejon, 305-764, South Korea, and the
- (3)Department of Biology, Chungang University, Seoul, 156-756, South Korea
- § To whom correspondence should be addressed: Dept. of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejon, 305-701, South Korea. Tel.: 82-42-869-4017; Fax: 82-42-869-2610.
Abstract
The biochemical role of poly(ADP-ribosyl)ation on internucleosomal DNA fragmentation associated with apoptosis was investigated in HL 60 human premyelocytic leukemia cells. It was found that UV light and chemotherapeutic drugs including adriamycin, mitomycin C, and cisplatin increased poly(ADP-ribosyl)ation of nuclear proteins, particularly histone H1. A poly(ADP-ribose) polymerase inhibitor, 3-aminobenzamide, prevented both internucleosomal DNA fragmentation and histone H1 poly(ADP-ribosyl)ation in cells treated with the apoptosis inducers. When nuclear chromatin was made accessible to the exogenous nuclease in a permeabilized cell system, chromatin of UV-treated cells was more susceptible to micrococcal nuclease than the chromatin of control cells. Suppression of histone H1 poly(ADP-ribosyl)ation by 3-aminobenzamide reduced the micrococcal nuclease digestibility of internucleosomal chromatin in UV-treated cells. These results suggest that the poly(ADP-ribosyl)ation of histone H1 correlates with the internucleosomal DNA fragmentation during apoptosis mediated by DNA damaging agents. This suggestion is supported by the finding that xeroderma pigmentosum cells which are defective in introducing incision at the site of DNA damage, failed to induce DNA fragmentation as well as histone H1 poly(ADP-ribosyl)ation after UV irradiation. We propose that poly(ADP-ribosyl)ation of histone H1 protein in the early stage of apoptosis facilitates internucleosomal DNA fragmentation by increasing the susceptibility of chromatin to cellular endonuclease.
Footnotes
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↵* This work was supported in part by a grant from the Korea Science and Engineering Foundation and by a grant from Science Research Center for Cell Differentiation, Seoul National University, Seoul, Korea. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 The abbreviations used are:
- PARP
-
poly(ADP-ribose) polymerase
- 3-AB
-
3-aminobenzamide
- XP
-
xeroderma pigmentosum
- PAGE
-
polyacrylamide gel electrophoresis.
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- Received November 21, 1995.
- Revision received January 22, 1996.
- © 1996 by The American Society for Biochemistry and Molecular Biology, Inc.
