title: Facilitation of base excision repair by chromatin remodeling.
abstract: Base Excision Repair (BER) is a conserved, intracellular DNA repair system that recognizes and removes chemically modified bases to insure genomic integrity and prevent mutagenesis. Aberrant BER has been tightly linked with a broad spectrum of human pathologies, such as several types of cancer, neurological degeneration, developmental abnormalities, immune dysfunction and aging. In the cell, BER must recognize and remove DNA lesions from the tightly condensed, protein-coated chromatin. Because chromatin is necessarily refractory to DNA metabolic processes, like transcription and replication, the compaction of the genomic material is also inhibitory to the repair systems necessary for its upkeep. Multiple ATP-dependent chromatin remodelling (ACR) complexes play essential roles in modulating the protein-DNA interactions within chromatin, regulating transcription and promoting activities of some DNA repair systems, including double-strand break repair and nucleotide excision repair. However, it remains unclear how BER operates in the context of chromatin, and if the chromatin remodelling processes that govern transcription and replication also actively regulate the efficiency of BER. In this review we highlight the emerging role of ACR in regulation of BER.
authors.affiliation: School of Molecular Biosciences, Washington State University, Pullman, WA 99164-7520, USA. Electronic address: jmhinz@wsu.edu.
authors.forename: John M
authors.initials: JM
authors.lastname: Hinz
authors.affiliation: Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602-7229, USA.
authors.forename: Wioletta
authors.initials: W
authors.lastname: Czaja
mesh_terms: D042002:Chromatin Assembly and Disassembly; D004247:DNA / Q000378:metabolism*; D004260:DNA Repair; D006801:Humans
chemical_list: D004247:DNA
keywords: AP endonuclease; BRG1; Chromatin remodeling; DNA damage; Glycosylase; INO80; ISWI; Ligase; Nucleosomes; PARP-1; Polymerase β; RSC; SNF2; SWI/SNF