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Cutting Edge: DGYW/WRCH Is a Better Predictor of Mutability at G:C Bases in Ig Hypermutation Than the Widely Accepted RGYW/WRCY Motif and Probably Reflects a Two-Step Activation-Induced Cytidine Deaminase-Triggered Process
Open accessAbstract
A feature of Ig hypermutation is the presence of hypermutable DNA sequences that are preferentially found in the V regions of Ig genes. Among these, RGYW/WRCY is the most pronounced motif (G:C is a mutable position; R = A/G, Y = C/T, and W = A/T). However, a molecular basis for the high mutability of RGYW was not known until recently. The discovery that activation-induced cytidine deaminase targets the DNA encoding V regions, has enabled the analysis of its targeting properties when expressed outside of the context of hypermutation. We analyzed these data and found evidence that activation-induced cytidine deaminase is the major source of the RGYW mutable motif, but with a new twist: DGYW/WRCH (G:C is the mutable position; D = A/G/T, H = T/C/A) is a better descriptor of the Ig mutation hotspot than RGYW/WRCY. We also found evidence that a DNA repair enzyme may play a role in modifying the sequence of hypermutation hotspots.
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Cites
DNA polymerase η is an A-T mutator in somatic hypermutation of immunoglobulin variable genes
Zeng, X., Winter, D. B., Kasmer, C., Kraemer, K. H., Lehmann, A. R., & Gearhart, P. J. (2001) · Nature Immunology · doi:10.1038/88740 · Cited by 420
Somatic mutation hotspots correlate with DNA polymerase η error spectrum
Rogozin, I. B., Pavlov, Y. I., Bebenek, K., Matsuda, T., & Kunkel, T. A. (2001) · Nature Immunology · doi:10.1038/88732 · Cited by 298
Self-citation
Cited by
Chesi, M., Robbiani, D. F., Sebag, M., Chng, W. J., Affer, M., Tiedemann, R., Valdez, R., Palmer, S. E., Haas, S. S., Stewart, A. K., et al. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.01.007 · Cited by 393
Murray, F., Darzentas, N., Hadzidimitriou, A., Tobin, G., Boudjogra, M., Scielzo, C., Laoutaris, N., Karlsson, K., Baran-Marzsak, F., Tsaftaris, A., et al. (2008) · Blood · doi:10.1182/blood-2007-07-099564 · Cited by 334
Related Mechanisms of Antibody Somatic Hypermutation and Class Switch Recombination
Hwang*, J. K., Alt*, F. W., & Yeap, L.-S. (2015) · Microbiology Spectrum · doi:10.1128/microbiolspec.mdna3-0037-2014 · Cited by 126
Roles of DNA Polymerases in Replication, Repair, and Recombination in Eukaryotes
Pavlov, Y. I., Shcherbakova, P. V., & Rogozin, I. B. (2006) · International Review of Cytology · doi:10.1016/s0074-7696(06)55002-8 · Cited by 123
Self-citationRogozin, I. B., Lada, A. G., Goncearenco, A., Green, M. R., De, S., Nudelman, G., Panchenko, A. R., Koonin, E. V., & Pavlov, Y. I. (2016) · Scientific Reports · doi:10.1038/srep38133 · Cited by 33
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Metadata
- Authors
- Rogozin, I. B., & Diaz, M.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-03
- Volume
- 172
- Issue
- 6
- Pages
- 3382-3384
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1529282476
- Cited by
- 213
- References
- 2
- FWCI
- 5.03
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: Cutting Edge: DGYW/WRCH Is a Better Predictor of Mutability at G:C Bases in Ig Hypermutation Than the Widely Accepted RGYW/WRCY Motif and Probably Reflects a Two-Step Activation-Induced Cytidine Deaminase-Triggered Process. https://app.cochat.ai/papers/10.4049/jimmunol.172.6.3382
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- Rogozin, I. B., & Diaz, M. (2004). Cutting Edge: DGYW/WRCH Is a Better Predictor of Mutability at G:C Bases in Ig Hypermutation Than the Widely Accepted RGYW/WRCY Motif and Probably Reflects a Two-Step Activation-Induced Cytidine Deaminase-Triggered Process. The Journal of Immunology. https://doi.org/10.4049/jimmunol.172.6.3382
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