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ATP-dependent chromatin remodeling in the DNA-damage response

DOI: 10.1186/1756-8935-5-4

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Abstract:

All living organisms depend on faithful preservation and transmission of genetic information to the next generation. Genetic information is stored within DNA, which is embedded in a dynamic nucleoprotein complex, called chromatin. The integrity of DNA is inescapably and continuously threatened by spontaneous and induced alterations to its basic structure. DNA itself is unstable and undergoes hydrolysis, which creates abasic sites and causes deamination [1]. Furthermore, cellular metabolic processes such as oxidative respiration produce oxygen radicals and other reactive molecules, which damage DNA [2]. Finally, exposure to environmental sources such as solar UV irradiation, × radiation, and numerous chemicals induces DNA injuries.DNA damage interferes with vital processes such as transcription and replication, which may cause cells to die or senesce, thus contributing to aging [3]. Replication of damaged DNA templates severely affects the fidelity of the polymerases, and may result in permanent mutations or chromosomal aberrations, which are at the basis of malignant transformation. Genetic erosion and its consequences are neutralized by a variety of DNA repair and associated DNA-damage signaling pathways, collectively called the DNA-damage response (DDR) [3-6]. In this review, we will focus on three repair pathways which are among the best characterized with regard to their repair mechanisms and interactions with chromatin: nucleotide excision repair (NER), which removes helix-distorting intra-strand lesions, and homologous recombination (HR) and non-homologous end-joining (NHEJ), both of which repair double-strand breaks (DSBs).All DNA-associated processes, such as transcription, replication, recombination, and DNA repair, are for a large part regulated by the chromatin structure [7,8]. Because this nucleoprotein complex limits the ability of other proteins to interact with DNA, the chromatin structure needs to be modified to facilitate efficient access to DNA. In

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