Induction of somatic hypermutation in immunoglobulin genes is dependent on DNA polymerase iota
- 31 October 2002
- journal article
- Published by Springer Nature in Nature
- Vol. 419 (6910) , 944-947
- https://doi.org/10.1038/nature01117
Abstract
Somatic hypermutation of immunoglobulin genes is a unique, targeted, adaptive process. While B cells are engaged in germinal centres in T-dependent responses, single base substitutions are introduced in the expressed Vh/Vl genes to allow the selection of mutants with a higher affinity for the immunizing antigen. Almost every possible DNA transaction has been proposed to explain this process, but each of these models includes an error-prone DNA synthesis step that introduces the mutations. The Y family of DNA polymerases--pol eta, pol iota, pol kappa and rev1--are specialized for copying DNA lesions and have high rates of error when copying a normal DNA template. By performing gene inactivation in a Burkitt's lymphoma cell line inducible for hypermutation, we show here that somatic hypermutation is dependent on DNA polymerase iota.Keywords
This publication has 29 references indexed in Scilit:
- AID-dependent somatic hypermutation occurs as a DNA single-strand event in the BL2 cell lineNature Immunology, 2002
- Error-Prone Repair DNA Polymerases in Prokaryotes and EukaryotesAnnual Review of Biochemistry, 2002
- Specialized DNA Polymerases, Cellular Survival, and the Genesis of MutationsScience, 2002
- Emerging links between hypermutation of antibody genes and DNA polymerasesNature Reviews Immunology, 2001
- 5'-Deoxyribose Phosphate Lyase Activity of Human DNA Polymerase ɩ in VitroScience, 2001
- Activation-Induced Cytidine Deaminase (AID) Deficiency Causes the Autosomal Recessive Form of the Hyper-IgM Syndrome (HIGM2)Cell, 2000
- Analysis of the targeting of the hypermutational machinery and the impact of subsequent selection on the distribution of nucleotide changes in human V rearrangementsImmunological Reviews, 1998
- Induction of Somatic Mutation in a Human B Cell Line In VitroImmunity, 1997
- Inactivation of the mouse Msh2 gene results in mismatch repair deficiency, methylation tolerance, hyperrecombination, and predisposition to cancerCell, 1995
- Herpes virus saimiri-transformed human T lymphocytes: normal functional phenotype and preserved T cell receptor signallingInternational Immunology, 1993