Tài liệu Báo cáo khoa học: Poly(ADP-ribose) The most elaborate metabolite of NAD+ Alexander Burkle

MINIREVIEW

Poly(ADP-ribose)

The most elaborate metabolite of NAD+

Alexander Bu¨rkle

Department of Biology, University of Konstanz, Germany

Introduction

The life cycle of poly(ADP-ribose)

NAD+ ⁄ NADH is among the most versatile biomole￾cules, as it can be used not only as a coenzyme for a

large number of oxidoreduction reactions, but in its

oxidized version can also serve as substrate for several

different of ADP-ribosyl transfer reactions, which are

the overarching theme of this minireview series. The

covalent transfer onto glutamic acid, aspartic acid or

lysine residues of target proteins (‘acceptors’), followed

by successive transfer reactions onto the protein–

mono(ADP-ribosyl) adduct, and subsequently onto the

emerging chain of several covalently linked ADP-ribo￾syl residues is the basis of the formation of poly(ADP￾ribose), which can be regarded the cell’s most elaborate

metabolite of NAD+ [1]. ADP-ribose chains may com￾prise up to 200 ADP-ribose units, coupled via unique

ribose (1¢¢fi2¢) ribose phosphate-phosphate linkages

and display several branching points resulting from the

formation of ribose (1¢¢¢fi2¢¢) ribose linkages (Fig. 1).

Poly(ADP-ribosyl)ation occurs in multicellular organ￾isms including plants and some lower unicellular eu￾karyotes, but is absent in prokaryotes and yeast.

Poly(ADP-ribosyl)ation is catalysed by the family of

poly(ADP-ribose) polymerases (PARPs; Fig. 2), enco￾ded in human cells by a set of 18 different genes [2].

Keywords

PARP; tankyrase; poly(ADP-ribose); DNA

damage; DNA repair; genomic instability;

centrosome; centromere; telomeres; mitotic

spindle

Correspondence

A. Bu¨rkle, Department of Biology,

Box X911, University of Konstanz,

D-78457 Konstanz, Germany

Tel: +49 7531 884035

Fax: +49 7531 884033

E-mail: [email protected]

Website: http://gutenberg.biologie.

uni-konstanz.de/

(Received 5 May 2005, accepted 14 July

2005)

doi:10.1111/j.1742-4658.2005.04864.x

One of the most drastic post-translational modification of proteins in eu￾karyotic cells is poly(ADP-ribosyl)ation, catalysed by a family enzymes

termed poly(ADP-ribose) polymerases (PARPs). In the human genome, 18

different genes have been identified that all encode PARP family members.

Poly(ADP-ribose) metabolism plays a role in a wide range of biological

structures and processes, including DNA repair and maintenance of

genomic stability, transcriptional regulation, centromere function and mito￾tic spindle formation, centrosomal function, structure and function of vault

particles, telomere dynamics, trafficking of endosomal vesicles, apoptosis

and necrosis. In this article, the most recent advances in this rapidly grow￾ing field are summarized.

Abbreviations

ANK, ankyrin; BER, base excision repair; BRCA1, breast cancer 1 protein; DBD, DNA-binding domain; HPS, His-Pro-Ser-rich; IRAP, insulin￾responsive amino peptidase; MVP, major vault protein; NuMa, nuclear mitotic apparatus protein; PARG, poly(ADP-ribose) glycohydrolase;

PARP, poly(ADP-ribose) polymerase; RNP, ribonucleoprotein particle; Sir2, silent information regulator 2; TCDD, 2,3,7,8-tetrachlorodibenzo￾p-dioxin; TRF, telomeric-repeat binding factor.

4576 FEBS Journal 272 (2005) 4576–4589 ª 2005 FEBS