Oxidized base damage and single-strand break repair in mammalian genomes: Role of disordered regions and posttranslational modifications in early enzymes

Research output: Contribution to journalArticle

46 Scopus citations

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.

Original languageEnglish
Pages (from-to)123-153
Number of pages31
JournalProgress in Molecular Biology and Translational Science
Volume110
DOIs
StatePublished - Jul 3 2012

Keywords

  • Base excision repair
  • Disordered terminal segments
  • DNA glycosylases
  • End-processing proteins
  • Posttranslational modifications
  • Reactive oxygen species
  • Repair complexes
  • Single-strand breaks

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine

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