Restriction of AID activity and somatic hypermutation by PARP-1
| Type of Publication: | Journal article |
| Publication status: | Published |
| URI (citable link): | http://nbn-resolving.de/urn:nbn:de:bsz:352-2-qflcz6didc1u6 |
| Author: | Tepper, Sandra; Mortusewicz, Oliver; Członka, Ewelina; Bello, Amanda; Schmidt, Angelika; Jeschke, Julia; Fischbach, Arthur; Pfeil, Ines; Mangerich, Aswin; Jungnickel, Berit et al. |
| Year of publication: | 2019 |
| Published in: | Nucleic Acids Research ; 47 (2019), 14. - pp. 7418-7429. - ISSN 0305-1048. - eISSN 1362-4962 |
| Pubmed ID: | 31127309 |
| DOI (citable link): | https://dx.doi.org/10.1093/nar/gkz466 |
| Summary: |
Affinity maturation of the humoral immune response depends on somatic hypermutation (SHM) of immunoglobulin (Ig) genes, which is initiated by targeted lesion introduction by activation-induced deaminase (AID), followed by error-prone DNA repair. Stringent regulation of this process is essential to prevent genetic instability, but no negative feedback control has been identified to date. Here we show that poly(ADP-ribose) polymerase-1 (PARP-1) is a key factor restricting AID activity during somatic hypermutation. Poly(ADP-ribose) (PAR) chains formed at DNA breaks trigger AID-PAR association, thus preventing excessive DNA damage induction at sites of AID action. Accordingly, AID activity and somatic hypermutation at the Ig variable region is decreased by PARP-1 activity. In addition, PARP-1 regulates DNA lesion processing by affecting strand biased A:T mutagenesis. Our study establishes a novel function of the ancestral genome maintenance factor PARP-1 as a critical local feedback regulator of both AID activity and DNA repair during Ig gene diversification.
|
| Subject (DDC): | 570 Biosciences, Biology |
| Link to License: | Attribution 4.0 International |
| Bibliography of Konstanz: | Yes |
| Refereed: | Yes |
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TEPPER, Sandra, Oliver MORTUSEWICZ, Ewelina CZŁONKA, Amanda BELLO, Angelika SCHMIDT, Julia JESCHKE, Arthur FISCHBACH, Ines PFEIL, Aswin MANGERICH, Berit JUNGNICKEL, 2019. Restriction of AID activity and somatic hypermutation by PARP-1. In: Nucleic Acids Research. 47(14), pp. 7418-7429. ISSN 0305-1048. eISSN 1362-4962. Available under: doi: 10.1093/nar/gkz466
@article{Tepper2019-08-22Restr-46006, title={Restriction of AID activity and somatic hypermutation by PARP-1}, year={2019}, doi={10.1093/nar/gkz466}, number={14}, volume={47}, issn={0305-1048}, journal={Nucleic Acids Research}, pages={7418--7429}, author={Tepper, Sandra and Mortusewicz, Oliver and Członka, Ewelina and Bello, Amanda and Schmidt, Angelika and Jeschke, Julia and Fischbach, Arthur and Pfeil, Ines and Mangerich, Aswin and Jungnickel, Berit} }
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