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Free Radic Biol Med. 2017 Jun;107:159-169. doi: 10.1016/j.freeradbiomed.2016.12.026. Epub 2016 Dec 20.

Chromatin associated mechanisms in base excision repair - nucleosome remodeling and DNA transcription, two key players.

Author information

1
Laboratoire de Biologie et Modélisation de la Cellule (LBMC) CNRS/ENSL/UCBL UMR 5239 and Institut NeuroMyoGène - INMG CNRS/UCBL UMR 5310, Université de Lyon, Ecole Normale Supérieure de Lyon, 69007 Lyon, France; Université de Grenoble Alpes/INSERM U1209/CNRS UMR 5309, 38042 Grenoble Cedex 9, France. Electronic address: herve.menoni@ens-lyon.fr.
2
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, CP 26077, CEP 05508-000 São Paulo, SP, Brazil.
3
Département de Médecine Nucléaire et de Radiobiologie, Université de Sherbrooke, Sherbrooke, Québec, Canada J1H 5N4.
4
Université de Grenoble Alpes/INSERM U1209/CNRS UMR 5309, 38042 Grenoble Cedex 9, France.
5
Laboratoire de Biologie et Modélisation de la Cellule (LBMC) CNRS/ENSL/UCBL UMR 5239 and Institut NeuroMyoGène - INMG CNRS/UCBL UMR 5310, Université de Lyon, Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Electronic address: dimitar.anguelov@ens-lyon.fr.

Abstract

Genomic DNA is prone to a large number of insults by a myriad of endogenous and exogenous agents. The base excision repair (BER) is the major mechanism used by cells for the removal of various DNA lesions spontaneously or environmentally induced and the maintenance of genome integrity. The presence of persistent DNA damage is not compatible with life, since abrogation of BER leads to early embryonic lethality in mice. There are several lines of evidences showing existence of a link between deficient BER, cancer proneness and ageing, thus illustrating the importance of this DNA repair pathway in human health. Although the enzymology of BER mechanisms has been largely elucidated using chemically defined DNA damage substrates and purified proteins, the complex interplay of BER with another vital process like transcription or when DNA is in its natural state (i.e. wrapped in nucleosome and assembled in chromatin fiber is largely unexplored. Cells use chromatin remodeling factors to overcome the general repression associated with the nucleosomal organization. It is broadly accepted that energy-dependent nucleosome remodeling factors disrupt histones-DNA interactions at the expense of ATP hydrolysis to favor transcription as well as DNA repair. Importantly, unlike transcription, BER is not part of a regulated developmental process but represents a maintenance system that should be efficient anytime and anywhere in the genome. In this review we will discuss how BER can deal with chromatin organization to maintain genetic information. Emphasis will be placed on the following challenging question: how BER is initiated within chromatin?

KEYWORDS:

8-oxoG; Base excision repair; Chromatin; Chromatin remodeling; DNA oxidative damage; Nucleosome; OGG1; Transcription coupled repair

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