Replication protein A interacts with AID to promote deamination of somatic hypermutation targets - PubMed (original) (raw)
. 2004 Aug 26;430(7003):992-8.
doi: 10.1038/nature02821. Epub 2004 Jul 25.
Affiliations
- PMID: 15273694
- DOI: 10.1038/nature02821
Free article
Replication protein A interacts with AID to promote deamination of somatic hypermutation targets
Jayanta Chaudhuri et al. Nature. 2004.
Free article
Abstract
Activation-induced cytidine deaminase (AID) is a single-stranded (ss) DNA deaminase required for somatic hypermutation (SHM) and class switch recombination of immunoglobulin genes. Class switch recombination involves transcription through switch regions, which generates ssDNA within R loops. However, although transcription through immunoglobulin variable region exons is required for SHM, it does not generate stable ssDNA, which leaves the mechanism of AID targeting unresolved. Here we characterize the mechanism of AID targeting to in-vitro-transcribed substrates harbouring SHM motifs. We show that the targeting activity of AID is due to replication protein A (RPA), a ssDNA-binding protein involved in replication, recombination and repair. The 32-kDa subunit of RPA interacts specifically with AID from activated B cells in a manner that seems to be dependent on post-translational AID modification. Thus, our study implicates RPA as a novel factor involved in immunoglobulin diversification. We propose that B-cell-specific AID-RPA complexes preferentially bind to ssDNA of small transcription bubbles at SHM 'hotspots', leading to AID-mediated deamination and RPA-mediated recruitment of DNA repair proteins.
Comment in
- Immunology: aid for AID.
Ramiro AR, Nussenzweig MC. Ramiro AR, et al. Nature. 2004 Aug 26;430(7003):980-1. doi: 10.1038/430980b. Nature. 2004. PMID: 15329709 No abstract available.
Similar articles
- The AID antibody diversification enzyme is regulated by protein kinase A phosphorylation.
Basu U, Chaudhuri J, Alpert C, Dutt S, Ranganath S, Li G, Schrum JP, Manis JP, Alt FW. Basu U, et al. Nature. 2005 Nov 24;438(7067):508-11. doi: 10.1038/nature04255. Epub 2005 Oct 26. Nature. 2005. PMID: 16251902 - Transcription-targeted DNA deamination by the AID antibody diversification enzyme.
Chaudhuri J, Tian M, Khuong C, Chua K, Pinaud E, Alt FW. Chaudhuri J, et al. Nature. 2003 Apr 17;422(6933):726-30. doi: 10.1038/nature01574. Epub 2003 Apr 9. Nature. 2003. PMID: 12692563 - Processive AID-catalysed cytosine deamination on single-stranded DNA simulates somatic hypermutation.
Pham P, Bransteitter R, Petruska J, Goodman MF. Pham P, et al. Nature. 2003 Jul 3;424(6944):103-7. doi: 10.1038/nature01760. Epub 2003 Jun 18. Nature. 2003. PMID: 12819663 - Activation-induced cytidine deaminase: a dual role in class-switch recombination and somatic hypermutation.
Durandy A. Durandy A. Eur J Immunol. 2003 Aug;33(8):2069-73. doi: 10.1002/eji.200324133. Eur J Immunol. 2003. PMID: 12884279 Review. - DNA targets of AID evolutionary link between antibody somatic hypermutation and class switch recombination.
Hackney JA, Misaghi S, Senger K, Garris C, Sun Y, Lorenzo MN, Zarrin AA. Hackney JA, et al. Adv Immunol. 2009;101:163-89. doi: 10.1016/S0065-2776(08)01005-5. Adv Immunol. 2009. PMID: 19231595 Review.
Cited by
- The Intriguing Mystery of RPA Phosphorylation in DNA Double-Strand Break Repair.
Fousek-Schuller VJ, Borgstahl GEO. Fousek-Schuller VJ, et al. Genes (Basel). 2024 Jan 27;15(2):167. doi: 10.3390/genes15020167. Genes (Basel). 2024. PMID: 38397158 Free PMC article. Review. - RPA guides UNG to uracil in ssDNA to facilitate antibody class switching and repair of mutagenic uracil at the replication fork.
Hayran AB, Liabakk NB, Aas PA, Kusnierczyk A, Vågbø CB, Sarno A, Iveland TS, Chawla K, Zahn A, Di Noia JM, Slupphaug G, Kavli B. Hayran AB, et al. Nucleic Acids Res. 2024 Jan 25;52(2):784-800. doi: 10.1093/nar/gkad1115. Nucleic Acids Res. 2024. PMID: 38000394 Free PMC article. - Activation-induced cytidine deaminase an antibody diversification enzyme interacts with chromatin modifier UBN1 in B-cells.
Jaiswal A, Roy R, Tamrakar A, Singh AK, Kar P, Kodgire P. Jaiswal A, et al. Sci Rep. 2023 Nov 10;13(1):19615. doi: 10.1038/s41598-023-46448-7. Sci Rep. 2023. PMID: 37949972 Free PMC article. - Mechanism and regulation of secondary immunoglobulin diversification.
Bello A, Hirth G, Voigt S, Tepper S, Jungnickel B. Bello A, et al. Cell Cycle. 2023 Sep;22(18):2070-2087. doi: 10.1080/15384101.2023.2275397. Epub 2023 Nov 23. Cell Cycle. 2023. PMID: 37909747 Review. - Role of the mechanisms for antibody repertoire diversification in monoclonal light chain deposition disorders: when a friend becomes foe.
Del Pozo-Yauner L, Herrera GA, Perez Carreon JI, Turbat-Herrera EA, Rodriguez-Alvarez FJ, Ruiz Zamora RA. Del Pozo-Yauner L, et al. Front Immunol. 2023 Jul 13;14:1203425. doi: 10.3389/fimmu.2023.1203425. eCollection 2023. Front Immunol. 2023. PMID: 37520549 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources