Chromatin Remodeling in Nucleotide Excision Repair in Mammalian Cells

The chromatin basic structure named nucleosome contains 147 DNA base pairs wounded 1.65 times around an octamer of histone proteins which consist of two copies of H2A, H2B, H3, and H4, separated by linker regions of 20-110 nucleotides. Nucleosome assem‐ bly in the nucleus proceeds in two stages. At first, hetero-tetramer H3/H4 integrates into the DNA and at the second stage the heterodimer H2A/H2B is added. Nucleosomes are further condensed into 30 nm fibers through the incorporation of histone H1, located in the linker regions, achieving an additional 250-fold structural compaction in metaphase chromosomes. Nucleosome packaging restricts protein binding and obstructs DNA-tem‐ plated reactions. Therefore, local modulation of DNA accessibility is necessary for the fundamental processes of transcription, replication and DNA repair to occur. In this sense, chromatin structure is not static but subject to changes at every level of its hierar‐ chy. Nucleosomes are considered dynamic and instructive particles that are involved in practically all chromosomal processes, being subjected to highly ordered changes consid‐ ered as epigenetic information, which modulates DNA accessibility [1, 2]. Nucleosomes exhibit three dynamic properties: a) covalent histone post-translational modifications, b) change of composition due to removal of histones and c) movement along DNA. The lat‐ ter two are carried out by ATP-dependent chromatin remodeling complexes [3]. Histone post-translational modifications (PTMs) such as the addition of acetyl, methyl, phos‐ phate, ubiquitin, and sumo groups change the properties of histones, modifying histoneDNA or histone-histone interactions [4]. Modifying complexes add or remove covalent modifications on particular residues of the Nand C-terminal domains of histone pro‐