ADP-Ribosylated Histone H1 from HeLa Cultures. Fundamental Differences to (ADP-Ribose)n-Histone H1 Conjugates Formed in vitro

Adamietz, Peter; Bredehorst, Reinhard; Hilz, Helmuth

doi:10.1111/j.1432-1033.1978.tb12682.x

Cited by 71 publications

(32 citation statements)

References 30 publications

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“…In addition, histone H1 (32,33) and high mobility group proteins (34) are also often poly(ADP-ribosyl)ated. It has been demonstrated that poly(ADP-ribosyl)ation of histone results in opening up of the chromatin structure (35,36).…”

Section: Discussionmentioning

confidence: 99%

A cellular defense pathway regulating transcription through poly(ADP-ribosyl)ation in response to DNA damage

Vispé

Yung

Ritchot

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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DNA damage is known to trigger key cellular defense pathways such as those involved in DNA repair. Here we provide evidence for a previously unrecognized pathway regulating transcription in response to DNA damage and show that this regulation is mediated by the abundant nuclear enzyme poly(ADP-ribose) polymerase. We found that poly(ADP-ribose) polymerase reduced the rate of transcription elongation by RNA polymerase II, suggesting that poly(ADP-ribose) polymerase negatively regulates transcription, possibly through the formation of poly(ADP-ribose) polymerase-RNA complexes. In damaged cells, poly(ADP-ribose) polymerase binds to DNA breaks and automodifies itself in the presence of NAD ؉ , resulting in poly(ADP-ribose) polymerase inactivation. We found that automodification of poly(ADP-ribose) polymerase in response to DNA damage resulted in the up-regulation of transcription, presumably because automodified poly-(ADP-ribose) polymerase molecules were released from transcripts, thereby relieving the block on transcription. Because agents that damage DNA damage RNA as well, up-regulation of RNA synthesis in response to DNA damage may provide cells with a mechanism to compensate for the loss of damaged transcripts and may be critical for cell survival after exposure to DNA-damaging agents. P oly(ADP-ribose) polymerase (PARP) is a highly abundant nuclear protein (for reviews, see refs. 1-6), the physiological role of which is not yet clear. In damaged cells, PARP binds to DNA breaks and becomes enzymatically activated (1, 5). In the presence of its substrate, NAD ϩ , activated PARP automodifies itself through the addition of ADP-ribosyl polymers (1, 5). This automodification inactivates PARP and leads to its dissociation from DNA breaks (7), a prerequisite for DNA repair (8-11). In contrast, in undamaged cells, PARP is found to be associated with regions actively transcribed by RNA polymerase II (POL II) (12), as well as with nucleoli, where ribosomal RNA is transcribed by RNA polymerase I (12). Furthermore, treatment of nuclei with RNase results in the release of PARP (13). In addition, exposure of cells to the transcription inhibitors 5,6-dichloro-1-␤-ribofuranosylbenzimidazole or actinomycin D disperses PARP from nucleoli (14). These observations suggest that PARP may play a role in transcription. Here we demonstrate that PARP mediates a link between DNA damage and elongation of transcription by RNA polymerase II. Materials and MethodsCell-Free Transcription͞DNA Repair Assay. Lymphoblastoid GMO1953C cells (NIGMS Human Mutant Cell Repository, NJ) were cultured in RPMI medium 1640, and whole cell-free extracts were prepared as described by Manley et al. (15). The reactions were carried out with 50 g of cell-free extract, 0.125 g of either pGf1a or p⌬Gf1a plasmid (16), and 0.125 g of ␥-irradiated pBluescript KS (ϩ) plasmid (pBS; Stratagene), prepared as described previously (10). The transcription-DNA repair assay reaction conditions have been described previously (16). Briefly, the reaction was carried out in a mix...

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Section: Discussionmentioning

confidence: 99%

A cellular defense pathway regulating transcription through poly(ADP-ribosyl)ation in response to DNA damage

Vispé

Yung

Ritchot

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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“…Thus, the apparent complexity of acceptor molecules observed in isolated nuclei may be lower in in situ nuclei, which is also observed in other modification reactions e.g. poly (ADP-ribosy1)ation [24] and phosphorylation [25]. This view is supported by the finding that treatment of isolated nuclei with detergents which may alter the structure and compartementalization of acceptor proteins and enzymes results in an increased activity of the transfer system.…”

Section: Discussionmentioning

confidence: 82%

Amino‐acid‐transfer reactions in isolated nuclei of Ehrlich ascites tumor cells

Rothbarth

Werner

1986

European Journal of Biochemistry

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Nuclear enzymatic activities incorporating amino acids into acid-insoluble material were investigated with respect to their differentiation from protein biosynthesis, reaction optima, requisites and localization. The product of the reaction was analyzed with respect to its localization and nature.(1) The nuclear activities are not inhibited by a number of inhibitors for protein biosynthesis. (2) The reaction optima found are similar to those of other residual nuclear syntheses including the stringent dependence on ATP. (3) All naturally occurring amino acids are utilized with different efficiencies. Their incorporation is neither cooperative nor competitive which points to individual incorporation mechanisms. Aminoacylation of tRNA may be involved because the incorporation is RNase-sensitive and aminoacylation of tRNA can be shown under the reaction conditions. (4) The enzymatic activities are exclusively nuclear. Significant activity with unchanged characteristics is released by sonication. (5) 70% of the radiolabel incorporated is exported across the nuclear envelope during the incubation. The residual 30% of the radiolabel is distributed without enrichment in any nuclear subfraction. (6) The products are exclusively of polypeptide nature. Since distinct nuclear proteins (e.g. histones) which are definitely preformed in the cytoplasm by protein biosynthesis become radiolabelled by the incorporation of radiolabelled amino acids, it is evident that the incorporation takes place at preformed polypeptides. This is unequivocally proven by the incorporation of radiolabelled amino acids into exogenous proteins by means of the solubilized nuclear activities.The results indicate that the nuclear activity under investigation reflects a nuclear modification system for polypeptides which may be of similar importance as other post-translational modification systems.

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“…Thus, a chromatin-associated poly(ADPribose) polymerase can catalyse the transfer of the ADP-ribose moiety of NAD to acceptor proteins and the subsequent elongation of the protein-attached monomer to a polymer (Kawaichi et al, 1980). The enzyme has been shown to be capable of both auto-modification (Yoshihara et al, 1981 ;Kawaichi et al, 1981) and modification of histones H1, H2a, H2b and H3 in vitro (Jump et al, 1980;K awaichi et al, 1980) and H 1 in vivo (Ueda et al, 1975;Adamietz et al, 1978). It has also been implicated in cellular recovery from DNA damage (Durkacz et al, 1980;Durkacz et al, 1981 a, b;Sims et al, 1982) and may regulate DNA ligase activity (Creissen & Shall, 1982) as well as participating in shut-down of scheduled DNA synthesis after DNA damage (Edwards & Taylor, 1980).…”

Section: Discussionmentioning

confidence: 99%