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

Muralidhar L. Hegde, Tadahide Izumi, Sankar Mitra

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

55 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
Title of host publicationProgress in Molecular Biology and Translational Science
Pages123-153
Number of pages31
DOIs
StatePublished - 2012

Publication series

NameProgress in Molecular Biology and Translational Science
Volume110
ISSN (Print)1877-1173

Bibliographical note

Funding Information:
The research in the authors’ laboratory has been supported by USPHS grants R01 CA81063 (S. M.), R01 CA53791 (S. M.), P01CA92854 (S. M.), and R01 CA98664 (T. I.). This review with limited focus is not meant to provide a comprehensive coverage of the literature, and many appropriate references could not be included for which the authors apologize. We thank Drs. Tapas K. Hazra (Department of Internal Medicine) and Istvan Boldogh (Department of Microbiology and Immunology) at the University of Texas Medical Branch for careful reading of the manuscript.

Keywords

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

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

Fingerprint

Dive into the research topics of 'Oxidized base damage and single-strand break repair in mammalian genomes: Role of disordered regions and posttranslational modifications in early enzymes'. Together they form a unique fingerprint.

Cite this