Related Experiment Video
Updated: Aug 6, 2026

Assessing Somatic Hypermutation in Ramos B Cells after Overexpression or Knockdown of Specific Genes
Published on: November 1, 2011
The translesion DNA polymerase zeta plays a major role in Ig and bcl-6 somatic hypermutation
1Division of Molecular Immunology, Department of Pathology, Cornell University Weill Medical College, New York, NY 10021, USA.
Abstract:
Ig somatic mutations would be introduced by a polymerase (pol) while repairing DNA outside main DNA replication. We show that human B cells constitutively express the translesion pol zeta, which effectively extends DNA past mismatched bases (mispair extender), and pol eta, which bypasses DNA lesions in an error-free fashion. Upon B cell receptor (BCR) engagement and coculture with activated CD4+ T cells, these lymphocytes upregulated pol zeta, downregulated pol eta, and mutated the Ig and bcl-6 genes. Inhibition of the pol zeta REV3 catalytic subunit by specific phosphorothioate-modified oligonucleotides impaired Ig and bcl-6 hypermutation and UV damage-induced DNA mutagenesis, without affecting cell cycle or viability. Thus, pol zeta plays a critical role in Ig and bcl-6 hypermutation, perhaps facilitated by the downregulation of pol eta.
Related Concept Videos
Proofreading
Mismatch Repair
Translesion DNA Polymerases
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
Conservative Site-specific Recombination and Phase Variation
The recognition sites for Cre recombinase called LoxP...
Proofreading
Errors During Replication are Corrected by the DNA Polymerase Enzyme
Mismatch Repair
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...

