Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Somatic hypermutation: subverted DNA repair.

Stella A Martomo1, Patricia J Gearhart

  • 1Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.

Current Opinion in Immunology
|April 18, 2006
PubMed
Summary

Somatic hypermutation uses DNA repair proteins to create antibody diversity. These proteins, instead of fixing DNA damage, recruit error-prone polymerases, increasing antibody mutation rates for pathogen defense.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Hunting for an Antigen: Humoral Immunity in Alzheimer's Disease.

Cells·2026
Same author

PD-1-targeted IL-15 mutein activates CD8+ and CD4+ T cells in infection and cancer.

JCI insight·2026
Same author

B cell receptor stimulation inhibits class switch recombination through elevated DNA repair.

DNA repair·2026
Same author

Generation and characterization of a tamoxifen-inducible, Cre driver rat for transgene expression in microglia.

Scientific reports·2025
Same author

EVOLVE platform, a trispecific T cell engager with integrated CD2 costimulation, for the treatment of solid and hematologic tumors.

Proceedings of the National Academy of Sciences of the United States of America·2025
Same author

Generation and characterization of a tamoxifen-inducible, Cre driver rat for transgene expression in microglia.

Research square·2025

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Somatic hypermutation is crucial for generating high-affinity antibodies that protect against pathogens.
  • The precise molecular mechanisms, particularly the roles of DNA repair proteins, are under investigation.

Purpose of the Study:

  • To elucidate the roles of specific DNA repair proteins in the somatic hypermutation pathway.
  • To understand how these proteins influence the fidelity of DNA synthesis during antibody diversification.

Main Methods:

  • Analysis of mutation types in gene-deficient mice.
  • Investigation of the interactions between activation-induced cytosine deaminase, uracil DNA glycosylase, MutS homologue 2, and MutS homologue 6.
  • Assessment of DNA polymerase recruitment and activity.

Related Experiment Videos

Main Results:

  • Activation-induced cytosine deaminase initiates hypermutation by creating uracil in DNA.
  • Uracils are recognized by uracil DNA glycosylase and mismatch repair proteins (MutS homologue 2 and MutS homologue 6).
  • These repair proteins, rather than repairing uracil, attract low-fidelity DNA polymerases, leading to extensive nucleotide substitutions.

Conclusions:

  • DNA repair proteins play a critical, non-canonical role in somatic hypermutation by promoting error-prone DNA synthesis.
  • This mechanism significantly expands antibody diversity, enhancing the immune response to pathogens.