Antibody diversification caused by disrupted mismatch repair and promiscuous DNA polymerases

Kimberly J. Zanotti, Patricia J. Gearhart

Research output: Contribution to journalArticle

Abstract

The enzyme activation-induced deaminase (AID) targets the immunoglobulin loci in activated B cells and creates DNA mutations in the antigen-binding variable region and DNA breaks in the switch region through processes known, respectively, as somatic hypermutation and class switch recombination. AID deaminates cytosine to uracil in DNA to create a U:G mismatch. During somatic hypermutation, the MutSα complex binds to the mismatch, and the error-prone DNA polymerase η generates mutations at A and T bases. During class switch recombination, both MutSα and MutLα complexes bind to the mismatch, resulting in double-strand break formation and end-joining. This review is centered on the mechanisms of how the MMR pathway is commandeered by B cells to generate antibody diversity.

Original languageEnglish (US)
Pages (from-to)110-116
Number of pages7
JournalDNA Repair
Volume38
DOIs
StatePublished - Feb 1 2016
Externally publishedYes

Fingerprint

DNA Mismatch Repair
DNA-Directed DNA Polymerase
Genetic Recombination
Repair
B-Lymphocytes
Antibody Diversity
Switches
Mutation
DNA Breaks
Enzyme Activation
Uracil
Antibodies
Cytosine
DNA
Cells
Immunoglobulins
Antigens
Joining
Enzymes
AICDA (activation-induced cytidine deaminase)

Keywords

  • Activation-induced deaminase
  • Class switch recombination
  • DNA polymerase η
  • Mismatch repair
  • Somatic hypermutation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Antibody diversification caused by disrupted mismatch repair and promiscuous DNA polymerases. / Zanotti, Kimberly J.; Gearhart, Patricia J.

In: DNA Repair, Vol. 38, 01.02.2016, p. 110-116.

Research output: Contribution to journalArticle

Zanotti, Kimberly J. ; Gearhart, Patricia J. / Antibody diversification caused by disrupted mismatch repair and promiscuous DNA polymerases. In: DNA Repair. 2016 ; Vol. 38. pp. 110-116.
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