DNA polymerases and somatic hypermutation of immunoglobulin genes

Mineaki Seki, Patricia J. Gearhart, Richard D. Wood

Research output: Contribution to journalArticle

Abstract

Somatic hypermutation of immunoglobulin variable genes, which increases antibody diversity, is initiated by the activation-induced cytosine deaminase (AID) protein. The current DNA-deamination model posits that AID deaminates cytosine to uracil in DNA, and that mutations are generated by DNA polymerases during replication or repair of the uracil residue. Mutations could arise as follows: by DNA replicating past the uracil; by removing the uracil with a uracil glycosylase and replicating past the resulting abasic site with a low-fidelity polymerase; or by repairing the uracil and synthesizing a DNA-repair patch downstream using a low-fidelity polymerase. In this review, we summarize the biochemical properties of specialized DNA polymerases in mammalian cells and discuss their participation in the mechanisms of hypermutation. Many recent studies have examined mice deficient in the genes that encode various DNA polymerases, and have shown that DNA polymerase H (POLH) contributes to hypermutation, whereas POLI, POLK and several other enzymes do not have major roles. The low-fidelity enzyme POLQ has been proposed as another candidate polymerase because it can efficiently bypass abasic sites and recent evidence indicates that it might participate in hypermutation.

Original languageEnglish (US)
Pages (from-to)1143-1148
Number of pages6
JournalEMBO Reports
Volume6
Issue number12
DOIs
StatePublished - Dec 2005
Externally publishedYes

Fingerprint

Immunoglobulin Genes
Uracil
DNA-Directed DNA Polymerase
Immunoglobulins
Genes
Cytosine Deaminase
DNA
Repair
Antibody Diversity
Chemical activation
Deamination
Mutation
Cytosine
Enzymes
DNA Repair
Cells
Antibodies
Proteins

Keywords

  • AID
  • Bypass
  • DNA polymerase
  • POLO
  • Somatic hypermutaion
  • Translesion

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

DNA polymerases and somatic hypermutation of immunoglobulin genes. / Seki, Mineaki; Gearhart, Patricia J.; Wood, Richard D.

In: EMBO Reports, Vol. 6, No. 12, 12.2005, p. 1143-1148.

Research output: Contribution to journalArticle

Seki, Mineaki ; Gearhart, Patricia J. ; Wood, Richard D. / DNA polymerases and somatic hypermutation of immunoglobulin genes. In: EMBO Reports. 2005 ; Vol. 6, No. 12. pp. 1143-1148.
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