Review: Modulation of chromatin structure by poly(ADP-ribosyl)ation

Abstract

Poly(ADP-ribose) polymerase is a nuclear enzyme that is highly conserved in eucaryotes. Its activity is totally dependent on the presence of DNA containing single or double stranded breaks. We have shown that this activation results in a decondensation of chromatin superstructure in vitro, which is caused mainly by hyper(ADP-ribosy)ation of histone H1. In core particles, the modification of histone H2B leads to a partial dissociation of DNA from core histones. The conformational change of native chromatin by poly(ADP-ribosyl)ation is reversible upon degradation of the histone H1-bound poly(ADP-ribose) by poly(ADP-ribose) glycohydrolase. We propose that cuts produced in vivo on DNA during DNA repair activate poly(ADP-ribose) polymerase, which then synthesizes poly(ADP-ribose) on histone H1, in particular, and contributes to the opening of the 25-nm chromatin fiber, resulting in the increased accessibility of DNA to excision repair enzymes. This mechanism is fast and reversible.

Centromere Proteins Cenpa, Cenpb, and Bub3 Interact with Poly(ADP-ribose) Polymerase-1 Protein and Are Poly(ADP-ribosyl)ated

“…Poly(ADP-ribosyl)ation of proteins by PARP-1 is a conserved post-translational modification implicated in DNA repair, apoptosis, regulation of transcription, anti-recombination, scaffold attachment, and modulation of chromatin structure (33,45,47,(77)(78)(79)(80)(81). We have previously demonstrated the association of PARP-1 with mammalian centromeric DNA and active centromeres, providing circumstantial evidence for PARP-1 function at the centromere (62).…”

“…Poly(ADP-ribose) polymerase-1 (PARP-1) 1 is a multifunctional enzyme that catalyzes the formation of poly(ADP-ribose) polymers on acceptor proteins involved in the maintenance of chromatin structure and DNA repair (31)(32)(33)(34)(35)(36)(37). The addition of poly(ADP-ribose) units makes the acceptor proteins more negatively charged, thus altering their structure, function, and binding properties to DNA (38 -40).…”

The PARP superfamily

“…In response to DNA damage, DNA-damage-dependent PARPs detect (75) and signal interruptions in the double helix. DNA-break-induced poly(ADP-ribosyl)ation of histone H1 and PARPs leading, in a few seconds, to the relaxation of chromatin structure (12,76) and simultaneously to the recruitment of XRCC1 (47) and SSBR enzymes to the damage site, thus increasing the repair kinetics. The native chromatin structure (30 nm fibre) is finally restored after degradation of PAR by PARG.…”

DNA damage and repair in tumour and non-tumour tissues of mice induced by nicotinamide

“…The enzyme activity has been associated with DNA repair, apoptosis, cell proliferation, cell differentiation and genome surveillance (Althaus and Richter, 1987;Satoh et al, 1994;Kaufman et al, 1993;Dai et al, 1987). PARP is activated by DNA strand breaks, which results in consumption of NAD (Jonsson et al, 1984b;Rawling et al, 1993) by producing longbranched polymers of the ADP-ribose moieties and free NAM (De Murcia et al, 1988). NAM, benzamide and 3-aminobenzamide (3aBAM) are all potent inhibitors of PARP at doses above 10-100uM (Rankin et al, 1989) by preventing production of polymer and reduction of the NAD pool after induction of DNA damage (Lautier et al, 1990(Lautier et al, , 1994Uchida et al, 1988).…”