title: Oxidized base damage and single-strand break repair in mammalian genomes: role of disordered regions and posttranslational modifications in early enzymes.
abstract: Oxidative genome damage induced by reactive oxygen species includes oxidized bases, abasic (AP) sites, and single-strand breaks, all of which are repaired via the evolutionarily conserved base excision repair/single-strand break repair (BER/SSBR) pathway. BER/SSBR in mammalian cells is complex, with preferred and backup sub-pathways, and is linked to genome replication and transcription. The early BER/SSBR enzymes, namely, DNA glycosylases (DGs) and the end-processing proteins such as abasic endonuclease 1 (APE1), form complexes with downstream repair (and other noncanonical) proteins via pairwise interactions. Furthermore, a unique feature of mammalian early BER/SSBR enzymes is the presence of a disordered terminal extension that is absent in their Escherichia coli prototypes. These nonconserved segments usually contain organelle-targeting signals, common interaction interfaces, and sites of posttranslational modifications that may be involved in regulating their repair function including lesion scanning. Finally, the linkage of BER/SSBR deficiency to cancer, aging, and human neurodegenerative diseases, and therapeutic targeting of BER/SSBR are discussed.
authors: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA.
authors: Muralidhar L
authors: ML
authors: Hegde
authors: Tadahide
authors: T
authors: Izumi
authors: Sankar
authors: S
authors: Mitra
mesh_terms: D000818:Animals; D053904:DNA Breaks, Single-Stranded; D004260:DNA Repair / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000378:metabolism*; D016678:Genome / Q000235:genetics*; D006801:Humans; D008322:Mammals / Q000235:genetics*; D010084:Oxidation-Reduction; D011499:Protein Processing, Post-Translational / Q000235:genetics*
chemical_list: D045643:DNA Repair Enzymes