Functions of disordered regions in mammalian early base excision repair proteins

Muralidhar L. Hegde, Tapas K. Hazra, Sankar Mitra

Research output: Contribution to journalReview article

44 Scopus citations

Abstract

Reactive oxygen species, generated endogenously and induced as a toxic response, produce several dozen oxidized or modified bases and/or single-strand breaks in mammalian and other genomes. These lesions are predominantly repaired via the conserved base excision repair (BER) pathway. BER is initiated with excision of oxidized or modified bases by DNA glycosylases leading to formation of abasic (AP) site or strand break at the lesion site. Structural analysis by experimental and modeling approaches shows the presence of a disordered segment commonly localized at the N- or C-terminus as a characteristic signature of mammalian DNA glycosylases which is absent in their bacterial prototypes. Recent studies on unstructured regions in DNA metabolizing proteins have indicated their essential role in interaction with other proteins and target DNA recognition. In this review, we have discussed the unique presence of disordered segments in human DNA glycosylases, and AP endonuclease involved in the processing of glycosylase products, and their critical role in regulating repair functions. These disordered segments also include sites for posttranslational modifications and nuclear localization signal. The teleological basis for their structural flexibility is discussed.

Original languageEnglish (US)
Pages (from-to)3573-3587
Number of pages15
JournalCellular and Molecular Life Sciences
Volume67
Issue number21
DOIs
StatePublished - Nov 1 2010

Keywords

  • Base excision repair
  • DNA glycosylases
  • Disordered terminal segments
  • End processing proteins
  • Protein-protein and protein-DNA interactions
  • Reactive oxygen species
  • Repair complex
  • Single strand breaks

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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