Sökning: onr:"swepub:oai:prod.swepub.kib.ki.se:141755636" >
Restriction of AID ...
Restriction of AID activity and somatic hypermutation by PARP-1
-
Tepper, S (författare)
-
- Mortusewicz, O (författare)
- Karolinska Institutet
-
Czlonka, E (författare)
-
visa fler...
-
Bello, A (författare)
-
Schmidt, A (författare)
-
Jeschke, J (författare)
-
Fischbach, A (författare)
-
Pfeil, I (författare)
-
Petersen-Mahrt, SK (författare)
-
Mangerich, A (författare)
-
- Helleday, T (författare)
- Karolinska Institutet
-
Leonhardt, H (författare)
-
Jungnickel, B (författare)
-
visa färre...
-
(creator_code:org_t)
- 2019-05-25
- 2019
- Engelska.
-
Ingår i: Nucleic acids research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 47:14, s. 7418-7429
- Relaterad länk:
-
https://academic.oup...
-
visa fler...
-
http://kipublication...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- 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.
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Tepper, S
-
Mortusewicz, O
-
Czlonka, E
-
Bello, A
-
Schmidt, A
-
Jeschke, J
-
visa fler...
-
Fischbach, A
-
Pfeil, I
-
Petersen-Mahrt, ...
-
Mangerich, A
-
Helleday, T
-
Leonhardt, H
-
Jungnickel, B
-
visa färre...
- Artiklar i publikationen
-
Nucleic acids re ...
- Av lärosätet
-
Karolinska Institutet