Mechanism of a genetic glissando: structural biology of indel mutations

Trends Biochem Sci. 2006 Apr;31(4):206-14. doi: 10.1016/j.tibs.2006.02.004. Epub 2006 Mar 20.

Abstract

Insertions and deletions of bases in DNA (collectively termed "indels") are both common and biologically relevant, being associated with different human pathologies including cancer and diseases associated with expansions of repeats. Four decades of research have resulted in several hypotheses regarding how indels are generated during DNA synthesis and how they subsequently undergo or escape correction. Recent structural studies of DNA polymerases bound to mutagenic substrates have increased our understanding of how DNA polymerases cope with abnormal substrates. These structures provide insight into the molecular mechanisms underlying indel generation.

Publication types

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

MeSH terms

  • DNA / biosynthesis*
  • DNA Damage
  • DNA-Directed DNA Polymerase / genetics*
  • Gene Deletion*
  • Humans
  • Models, Genetic
  • Mutagenesis, Insertional*
  • Mutation
  • Nucleic Acid Conformation

Substances

  • DNA
  • DNA-Directed DNA Polymerase