Error-prone candidates vie for somatic mutation - PubMed (original) (raw)
Comment
Error-prone candidates vie for somatic mutation
V Poltoratsky et al. J Exp Med. 2000.
No abstract available
Figures
Figure 1
A speculative mechanism for somatic V region hypermutation. I. An unusual cytidine deaminase might play a role in the introduction of abasic lesions (O) in DNA via conversion of C to U, followed by the removal of the U by uracil glycosylase (UDG1). RGYW/WRCY represent a hot spot template sequence (A/G, G, C/T, A/T), with a mutation occurring most frequently opposite the G/C. II. A high-fidelity processive replicative polymerase (pol δ) stalls at the abasic lesion, dissociates, and is replaced by a promiscuous nonprocessive polymerase, e.g., pol ι (shown in sketch), or by some other errant polymerase. After translesional synthesis resulting in a mutation opposite the lesion, pol ι dissociates, and processive synthesis resumes with pol δ. III. A subsequent round of replication results in a mixed population of B cell clones, some mutated and some not. Alternative mechanisms can be envisioned that do not involve the introduction of a lesion. Instead, an undamaged DNA template could be copied by a low-fidelity polymerase such as pol ι, causing mutations that are favored in the RGYW hot spot sequence.
Comment on
- Somatic hypermutation in the absence of DNA-dependent protein kinase catalytic subunit (DNA-PK(cs)) or recombination-activating gene (RAG)1 activity.
Bemark M, Sale JE, Kim HJ, Berek C, Cosgrove RA, Neuberger MS. Bemark M, et al. J Exp Med. 2000 Nov 20;192(10):1509-14. doi: 10.1084/jem.192.10.1509. J Exp Med. 2000. PMID: 11085752 Free PMC article.
Similar articles
- Somatic hypermutation in the absence of DNA-dependent protein kinase catalytic subunit (DNA-PK(cs)) or recombination-activating gene (RAG)1 activity.
Bemark M, Sale JE, Kim HJ, Berek C, Cosgrove RA, Neuberger MS. Bemark M, et al. J Exp Med. 2000 Nov 20;192(10):1509-14. doi: 10.1084/jem.192.10.1509. J Exp Med. 2000. PMID: 11085752 Free PMC article. - DNA double-strand break repair and V(D)J recombination: involvement of DNA-PK.
Jackson SP, Jeggo PA. Jackson SP, et al. Trends Biochem Sci. 1995 Oct;20(10):412-5. doi: 10.1016/s0968-0004(00)89090-8. Trends Biochem Sci. 1995. PMID: 8533154 Review. - RAG-1 and ATM coordinate monoallelic recombination and nuclear positioning of immunoglobulin loci.
Hewitt SL, Yin B, Ji Y, Chaumeil J, Marszalek K, Tenthorey J, Salvagiotto G, Steinel N, Ramsey LB, Ghysdael J, Farrar MA, Sleckman BP, Schatz DG, Busslinger M, Bassing CH, Skok JA. Hewitt SL, et al. Nat Immunol. 2009 Jun;10(6):655-64. doi: 10.1038/ni.1735. Nat Immunol. 2009. PMID: 19448632 Free PMC article. - V(D)J recombination catalyzed by mutant RAG proteins lacking consensus DNA-PK phosphorylation sites.
Lin JM, Landree MA, Roth DB. Lin JM, et al. Mol Immunol. 1999 Dec;36(18):1263-9. doi: 10.1016/s0161-5890(99)00099-1. Mol Immunol. 1999. PMID: 10684966 - How to make ends meet in V(D)J recombination.
Grawunder U, Harfst E. Grawunder U, et al. Curr Opin Immunol. 2001 Apr;13(2):186-94. doi: 10.1016/s0952-7915(00)00203-x. Curr Opin Immunol. 2001. PMID: 11228412 Review.
Cited by
- Genomic uracil homeostasis during normal B cell maturation and loss of this balance during B cell cancer development.
Shalhout S, Haddad D, Sosin A, Holland TC, Al-Katib A, Martin A, Bhagwat AS. Shalhout S, et al. Mol Cell Biol. 2014 Nov;34(21):4019-32. doi: 10.1128/MCB.00589-14. Epub 2014 Aug 25. Mol Cell Biol. 2014. PMID: 25154417 Free PMC article. - Stabilised DNA secondary structures with increasing transcription localise hypermutable bases for somatic hypermutation in IGHV3-23.
Duvvuri B, Duvvuri VR, Wu J, Wu GE. Duvvuri B, et al. Immunogenetics. 2012 Jul;64(7):481-96. doi: 10.1007/s00251-012-0607-3. Epub 2012 Mar 6. Immunogenetics. 2012. PMID: 22391874 - Mismatch-mediated error prone repair at the immunoglobulin genes.
Chahwan R, Edelmann W, Scharff MD, Roa S. Chahwan R, et al. Biomed Pharmacother. 2011 Dec;65(8):529-36. doi: 10.1016/j.biopha.2011.09.001. Epub 2011 Oct 24. Biomed Pharmacother. 2011. PMID: 22100214 Free PMC article. Review. - Mutator effects and mutation signatures of editing deaminases produced in bacteria and yeast.
Lada AG, Krick CF, Kozmin SG, Mayorov VI, Karpova TS, Rogozin IB, Pavlov YI. Lada AG, et al. Biochemistry (Mosc). 2011 Jan;76(1):131-46. doi: 10.1134/s0006297911010135. Biochemistry (Mosc). 2011. PMID: 21568845 Free PMC article. - Inaccurate DNA synthesis in cell extracts of yeast producing active human DNA polymerase iota.
Makarova AV, Grabow C, Gening LV, Tarantul VZ, Tahirov TH, Bessho T, Pavlov YI. Makarova AV, et al. PLoS One. 2011 Jan 31;6(1):e16612. doi: 10.1371/journal.pone.0016612. PLoS One. 2011. PMID: 21304950 Free PMC article.
References
- Harris R.S., Kong Q., Maizels N. Somatic hypermutation and the three R'srepair, replication and recombination. Mutat. Res. 1999;436:157–178. - PubMed
- Steele E.J., Rothenfluh H.S., Blanden R.V. Mechanism of antigen-driven somatic hypermutation of rearranged immunoglobulin V(D)J genes in the mouse. Immunol. Cell Biol. 1997;75:82–95. - PubMed
- Wilson P., Liu Y.J., Banchereau J., Capra J.D., Pascual V. Amino acid insertions and deletions contribute to diversify the human Ig repertoire. Immunol. Rev. 1998;162:143–151. - PubMed
- Jolly C.J., Wagner S.D., Rada C., Klix N., Milstein C., Neuberger M.S. The targeting of somatic hypermutation. Semin. Immunol. 1996;8:159–168. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
- GM42554/GM/NIGMS NIH HHS/United States
- 5T32CA09173/CA/NCI NIH HHS/United States
- T32 CA009173/CA/NCI NIH HHS/United States
- R01 GM021422/GM/NIGMS NIH HHS/United States
- GM21422/GM/NIGMS NIH HHS/United States
- R37 GM021422/GM/NIGMS NIH HHS/United States
LinkOut - more resources
Full Text Sources
Other Literature Sources