title: Accessing DNA damage in chromatin: Preparing the chromatin landscape for base excision repair.
abstract: DNA damage in chromatin comes in many forms, including single base lesions that induce base excision repair (BER). We and others have shown that the structural location of DNA lesions within nucleosomes greatly influences their accessibility to repair enzymes. Indeed, a difference in the location of uracil as small as one-half turn of the DNA backbone on the histone surface can result in a 10-fold difference in the time course of its removal in vitro. In addition, the cell has evolved several interdependent processes capable of enhancing the accessibility of excision repair enzymes to DNA lesions in nucleosomes, including post-translational modification of histones, ATP-dependent chromatin remodeling and interchange of histone variants in nucleosomes. In this review, we focus on different factors that affect accessibility of BER enzymes to nucleosomal DNA.
authors.affiliation: School of Molecular Biosciences, Washington State University, Pullman, WA 99164-7520, United States.
authors.forename: Yesenia
authors.initials: Y
authors.lastname: Rodriguez
authors.affiliation: School of Molecular Biosciences, Washington State University, Pullman, WA 99164-7520, United States.
authors.forename: John M
authors.initials: JM
authors.lastname: Hinz
authors.affiliation: School of Molecular Biosciences, Washington State University, Pullman, WA 99164-7520, United States. Electronic address: smerdon@vetmed.wsu.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Smerdon
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D019951:DNA Polymerase beta / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D014498:Uracil / Q000378:metabolism; D051981:Uracil-DNA Glycosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D006657:Histones; D009707:Nucleosomes; D014498:Uracil; D000255:Adenosine Triphosphate; D004247:DNA; D019951:DNA Polymerase beta; D051981:Uracil-DNA Glycosidase
keywords: AP endonuclease; Chromatin; Chromatin remodeling; Glycosylase; Histone acetylation; Histone variants; Ligase; Nucleosome dynamics; Polymerase β; Rotational setting