Damaged DNA binding protein 2 in reactive oxygen species (ROS) regulation and premature senescence

Int J Mol Sci. 2012;13(9):11012-11026. doi: 10.3390/ijms130911012. Epub 2012 Sep 5.

Abstract

Premature senescence induced by DNA damage or oncogene is a critical mechanism of tumor suppression. Reactive oxygen species (ROS) have been implicated in the induction of premature senescence response. Several pathological disorders such as cancer, aging and age related neurological abnormalities have been linked to ROS deregulation. Here, we discuss how Damaged DNA binding Protein-2 (DDB2), a nucleotide excision repair protein, plays an important role in ROS regulation by epigenetically repressing the antioxidant genes MnSOD and Catalase. We further revisit a model in which DDB2 plays an instrumental role in DNA damage induced ROS accumulation, ROS induced premature senescence and inhibition of skin tumorigenesis.

Keywords: DDB2; NER; apoptosis; reactive oxygen species; senescence.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Aging, Premature / genetics*
  • Animals
  • Apoptosis / genetics
  • Ataxia Telangiectasia Mutated Proteins / metabolism
  • Catalase / biosynthesis
  • Catalase / genetics
  • Cell Transformation, Neoplastic
  • Cellular Senescence / genetics*
  • Cullin Proteins / metabolism
  • DNA Damage / genetics*
  • DNA Repair / genetics
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Humans
  • Mice
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction / genetics
  • Skin Neoplasms / pathology
  • Superoxide Dismutase / biosynthesis
  • Superoxide Dismutase / genetics
  • Xeroderma Pigmentosum / genetics

Substances

  • CUL4A protein, human
  • Cullin Proteins
  • DDB1 protein, human
  • DDB2 protein, human
  • DNA-Binding Proteins
  • Reactive Oxygen Species
  • Catalase
  • Superoxide Dismutase
  • ATR protein, human
  • Ataxia Telangiectasia Mutated Proteins