Controlling somatic hypermutation in immunoglobulin variable and switch regions

Robert W. Maul, Patricia J. Gearhart

Research output: Contribution to journalReview articlepeer-review

Abstract

Activation-induced deaminase (AID) is a B-cell-specific enzyme required for initiating the mechanisms of affinity maturation and isotype switching of antibodies. AID functions by deaminating cytosine to uracil in DNA, which initiates a cascade of events resulting in mutations and strand breaks in the immunoglobulin loci. There is an intricate interplay between faithful DNA repair and mutagenic DNA repair during somatic hypermutation, in that some proteins from accurate repair pathways are also involved in mutagenesis. One factor that shifts the balance from faithful to mutagenic repair is the genomic sequence of the switch regions. Indeed, the sequence of the switch μ region is designed to maximize AID access to increase the abundance of clustered dU bases. The frequency and proximity of these dU nucleotides then in turn inhibit faithful repair and promote strand breaks.

Original languageEnglish (US)
Pages (from-to)113-122
Number of pages10
JournalImmunologic Research
Volume47
Issue number1-3
DOIs
StatePublished - Jul 2010
Externally publishedYes

Keywords

  • Activation-induced deaminase
  • Antibody diversity
  • DNA polymerase η
  • MSH2-MSH6
  • RNA polymerase II
  • Switch μ region
  • Uracil DNA glycosylase

ASJC Scopus subject areas

  • Immunology

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