Parp3 negatively regulates immunoglobulin class switch recombination.
To generate highly specific and adapted immune responses, B cells diversify their antibody repertoire through mechanisms involving the generation of programmed DNA damage. Somatic hypermutation (SHM) and class switch recombination (CSR) are initiated by the recruitment of activation-induced cytidine...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-05-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1005240 |
| _version_ | 1818735115950358528 |
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| author | Isabelle Robert Léa Gaudot Mélanie Rogier Vincent Heyer Aurélia Noll Françoise Dantzer Bernardo Reina-San-Martin |
| author_facet | Isabelle Robert Léa Gaudot Mélanie Rogier Vincent Heyer Aurélia Noll Françoise Dantzer Bernardo Reina-San-Martin |
| author_sort | Isabelle Robert |
| collection | DOAJ |
| description | To generate highly specific and adapted immune responses, B cells diversify their antibody repertoire through mechanisms involving the generation of programmed DNA damage. Somatic hypermutation (SHM) and class switch recombination (CSR) are initiated by the recruitment of activation-induced cytidine deaminase (AID) to immunoglobulin loci and by the subsequent generation of DNA lesions, which are differentially processed to mutations during SHM or to double-stranded DNA break intermediates during CSR. The latter activate the DNA damage response and mobilize multiple DNA repair factors, including Parp1 and Parp2, to promote DNA repair and long-range recombination. We examined the contribution of Parp3 in CSR and SHM. We find that deficiency in Parp3 results in enhanced CSR, while SHM remains unaffected. Mechanistically, this is due to increased occupancy of AID at the donor (Sμ) switch region. We also find evidence of increased levels of DNA damage at switch region junctions and a bias towards alternative end joining in the absence of Parp3. We propose that Parp3 plays a CSR-specific role by controlling AID levels at switch regions during CSR. |
| first_indexed | 2024-12-18T00:16:08Z |
| format | Article |
| id | doaj.art-4b9c303244a747d78f14181d498c6506 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-18T00:16:08Z |
| publishDate | 2015-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-4b9c303244a747d78f14181d498c65062022-12-21T21:27:31ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042015-05-01115e100524010.1371/journal.pgen.1005240Parp3 negatively regulates immunoglobulin class switch recombination.Isabelle RobertLéa GaudotMélanie RogierVincent HeyerAurélia NollFrançoise DantzerBernardo Reina-San-MartinTo generate highly specific and adapted immune responses, B cells diversify their antibody repertoire through mechanisms involving the generation of programmed DNA damage. Somatic hypermutation (SHM) and class switch recombination (CSR) are initiated by the recruitment of activation-induced cytidine deaminase (AID) to immunoglobulin loci and by the subsequent generation of DNA lesions, which are differentially processed to mutations during SHM or to double-stranded DNA break intermediates during CSR. The latter activate the DNA damage response and mobilize multiple DNA repair factors, including Parp1 and Parp2, to promote DNA repair and long-range recombination. We examined the contribution of Parp3 in CSR and SHM. We find that deficiency in Parp3 results in enhanced CSR, while SHM remains unaffected. Mechanistically, this is due to increased occupancy of AID at the donor (Sμ) switch region. We also find evidence of increased levels of DNA damage at switch region junctions and a bias towards alternative end joining in the absence of Parp3. We propose that Parp3 plays a CSR-specific role by controlling AID levels at switch regions during CSR.https://doi.org/10.1371/journal.pgen.1005240 |
| spellingShingle | Isabelle Robert Léa Gaudot Mélanie Rogier Vincent Heyer Aurélia Noll Françoise Dantzer Bernardo Reina-San-Martin Parp3 negatively regulates immunoglobulin class switch recombination. PLoS Genetics |
| title | Parp3 negatively regulates immunoglobulin class switch recombination. |
| title_full | Parp3 negatively regulates immunoglobulin class switch recombination. |
| title_fullStr | Parp3 negatively regulates immunoglobulin class switch recombination. |
| title_full_unstemmed | Parp3 negatively regulates immunoglobulin class switch recombination. |
| title_short | Parp3 negatively regulates immunoglobulin class switch recombination. |
| title_sort | parp3 negatively regulates immunoglobulin class switch recombination |
| url | https://doi.org/10.1371/journal.pgen.1005240 |
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