Somatic hypermutation and the three R's: Repair, replication and recombination

Reuben S. Harris, Qingzhong Kong, Nancy Maizels

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

Somatic hypermutation introduces single base changes into the rearranged variable (V) regions of antigen activated B cells at a rate of approximately 1 mutation per kilobase per generation. This is nearly a million-fold higher than the typical mutation rate in a mammalian somatic cell. Rampant mutation at this level could have a devastating effect, but somatic hypermutation is accurately targeted and tightly regulated. Here, we provide an overview of immunoglobulin gene somatic hypermutation; discuss mechanisms of mutation in model organisms that may be relevant to the hypermutation mechanism; and review recent advances toward understanding the possible role(s) of DNA repair, replication, and recombination in this fascinating process.

Original languageEnglish (US)
Pages (from-to)157-178
Number of pages22
JournalMutation Research - Reviews in Mutation Research
Volume436
Issue number2
DOIs
StatePublished - 1999

Bibliographical note

Funding Information:
R.S.H. is a fellow of the Natural Sciences and Engineering Research Council of Canada (NSERC). Our research on somatic hypermutation is supported by R01 GM41712 from the US National Institutes of Health.

Keywords

  • Affinity
  • Antibody
  • B cell
  • DNA repair
  • DNA replication
  • Germinal center
  • Immunoglobulin
  • Mismatch repair
  • Recombination
  • Selection
  • Somatic hypermutation

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