Review Chromatin-remodelling mechanisms in cancer Laura Lafon-Hughes a , Marı ´a Vittoria Di Tomaso a , Leticia Me ´ndez-Acun ˜a a , Wilner Martı ´nez-Lo ´pez a,b, * a Genetic Toxicology Department, Instituto de Investigaciones Biolo ´gicas Clemente Estable, Montevideo, Uruguay b Institute of Biology, Faculty of Sciences, Montevideo, Uruguay Received 12 April 2007; received in revised form 29 January 2008; accepted 29 January 2008 This paper has been dedicated to the memory of our friend and colleague Marı ´a Mu ¨hlmann. Abstract Chromatin-remodelling mechanisms include DNA methylation, histone-tail acetylation, poly-ADP-ribosylation, and ATP-dependent chro- matin-remodelling processes. Some epigenetic modifications among others have been observed in cancer cells, namely (1) local DNA hypermethylation and global hypomethylation, (2) alteration in histone acetylation/deacetylation balance, (3) increased or decreased poly- ADP-ribosylation, and (4) failures in ATP-dependent chromatin-remodelling mechanisms. Moreover, these alterations can influence the response to classical anti-tumour treatments. Drugs targeting epigenetic alterations are under development. Currently, DNA methylation and histone deacetylase inhibitors are in use in cancer therapy, and poly-ADP-ribosylation inhibitors are undergoing clinical trials. Epigenetic therapy is gaining in importance in pharmacology as a new tool to improve anti-cancer therapies. # 2008 Elsevier B.V. All rights reserved. Keywords: Epigenetics; DNA methylation; Histone acetylation; Poly-ADP-ribosylation; ATP-dependent chromatin remodelling; Cancer therapy Contents 1. Epigenetics and cancer .......................................................................... 000 2. DNA methylation.............................................................................. 000 2.1. DNA methyltransferases .................................................................... 000 2.2. DNA demethylase activities .................................................................. 000 2.3. Gene silencing and chromatin-remodelling associated to DNA methylation ................................. 000 2.4. Genome imprinting and X chromosome inactivation ................................................. 000 2.5. DNA methylation in carcinogenesis ............................................................ 000 2.6. Inhibitors of DNMTs and demethylases ......................................................... 000 3. Histone acetylation............................................................................. 000 3.1. Histone acetyltransferases ................................................................... 000 3.2. Histone deacetylases ....................................................................... 000 3.3. Histone acetylation in carcinogenesis ........................................................... 000 3.3.1. Alteration of histone acetyltransferases activity .............................................. 000 3.3.2. Alteration of histone deacetylases activity .................................................. 000 3.4. Histone deacetylases inhibitors ................................................................ 000 4. Poly-ADP-ribosylation .......................................................................... 000 4.1. Poly-ADP-ribosylation in carcinogenesis ......................................................... 000 4.2. PARP inhibitors .......................................................................... 000 www.elsevier.com/locate/reviewsmr Available online at www.sciencedirect.com Mutation Research xxx (2008) xxx–xxx * Corresponding author at: Genetic Toxicology Department, Instituto de Investigaciones Biolo ´gicas Clemente Estable, Avenida Italia 3318, CP 11.600, Montevideo, Uruguay. Tel.: +598 2 487 16 21x136; fax: +598 2 487 55 48. E-mail address: wlopez@iibce.edu.uy (W. Martı ´nez-Lo ´pez). + Models MUTREV-7881; No of Pages 24 1383-5742/$ – see front matter # 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.mrrev.2008.01.008 Please cite this article in press as: L. Lafon-Hughes, et al., Chromatin-remodelling mechanisms in cancer, Mutat. Res.: Rev. Mutat. Res. (2008), doi:10.1016/j.mrrev.2008.01.008