Mechanism of a genetic glissando: structural biology of indel mutations.
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.
Laboratory of Structural Biology and Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA.
Miguel
M
Garcia-Diaz
Thomas A
TA
Kunkel
D004247:DNA / Q000096:biosynthesis*; D004249:DNA Damage; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D008957:Models, Genetic; D016254:Mutagenesis, Insertional; D009154:Mutation; D009690:Nucleic Acid Conformation
D004247:DNA; D004259:DNA-Directed DNA Polymerase