PuSH - Publication Server of Helmholtz Zentrum München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Tepper, S.* ; Mortusewicz, O.* ; Członka, E.* ; Bello, A.* ; Schmidt, A.* ; Jeschke, J.* ; Fischbach, A.* ; Pfeil, I. ; Petersen-Mahrt, S.K.* ; Mangerich, A.* ; Helleday, T.* ; Leonhardt, H.* ; Jungnickel, B.*

Restriction of AID activity and somatic hypermutation by PARP-1.

Nucleic Acids Res. 47, 7418-7429 (2019)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
11.147
3.156
4
4
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Keywords Dna-repair; B-cells; Homologous Recombination; Genomic Instability; Gene Conversion; Deaminase Aid; Strand Bias; Poly(adp-ribose); Mechanisms; Transcription
Language english
Publication Year 2019
HGF-reported in Year 2019
ISSN (print) / ISBN 0305-1048
e-ISSN 1362-4962
Journal Nucleic Acids Research
Quellenangaben Volume: 47, Issue: 14, Pages: 7418-7429 Article Number: , Supplement: ,
Publisher Oxford University Press
Publishing Place Great Clarendon St, Oxford Ox2 6dp, England
Reviewing status Peer reviewed
Institute(s) Institute of Clinical Molecular Biology and Tumor Genetics (K.MOLBI)
POF-Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s) Immune Response and Infection
PSP Element(s) G-501490-001
DOI 10.1093/nar/gkz466
WOS ID WOS:000483815100026
Scopus ID 85071703542
PubMed ID 31127309
Erfassungsdatum 2019-05-29
[➜Report correction]