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Updated: Jan 24, 2026
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Analysis of Somatic Hypermutation in the JH4 intron of Germinal Center B cells from Mouse Peyer's Patches
Published on: April 20, 2021
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Restriction of AID activity and somatic hypermutation by PARP-1
Sandra Tepper1, Oliver Mortusewicz2,3, Ewelina Członka1
1Department of Cell Biology, Institute of Biochemistry and Biophysics, School of Biology and Pharmacy, Friedrich Schiller University, 07745 Jena, Germany.
Nucleic Acids Research
|May 26, 2019
Summary
Poly(ADP-ribose) polymerase-1 (PARP-1) restricts activation-induced deaminase (AID) activity during somatic hypermutation. This feedback mechanism prevents excessive DNA damage, ensuring immunoglobulin gene diversification and genome stability.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Affinity maturation of humoral immunity relies on somatic hypermutation (SHM) of immunoglobulin (Ig) genes.
- SHM initiation involves activation-induced deaminase (AID) and error-prone DNA repair, requiring strict regulation to prevent genetic instability.
- No negative feedback mechanism for AID activity in SHM had been previously identified.
Purpose of the Study:
- To investigate the role of poly(ADP-ribose) polymerase-1 (PARP-1) in regulating activation-induced deaminase (AID) activity during somatic hypermutation (SHM).
- To identify potential negative feedback controls for AID in the context of immunoglobulin gene diversification.
Main Methods:
- Investigated the interaction between PARP-1 and AID in the context of DNA breaks.
- Assessed the impact of PARP-1 activity on AID-induced DNA damage and SHM at Ig variable regions.
- Analyzed the effect of PARP-1 on DNA lesion processing and strand-biased mutagenesis.
Main Results:
- Poly(ADP-ribose) (PAR) chains generated at DNA breaks recruit and associate with AID, limiting its activity.
- PARP-1 activity was found to decrease AID activity and somatic hypermutation at Ig variable regions.
- PARP-1 influences DNA repair pathways, affecting strand-biased A:T mutagenesis during SHM.
Conclusions:
- PARP-1 acts as a critical local feedback regulator of AID activity during SHM.
- PARP-1's function in regulating AID and DNA repair is essential for immunoglobulin gene diversification.
- This study reveals a novel role for the genome maintenance factor PARP-1 in controlling immune gene adaptation.
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