Skip to Main content Skip to Navigation
New interface
Journal articles

Human Tribbles 3 Protects Nuclear DNA from Cytidine Deamination by APOBEC3A

Abstract : The human polydeoxynucleotide cytidine deaminases APOBEC3A, APOBEC3C, and APOBEC3H are capable of mutating viral DNA in the nucleus, whereas APOBEC3A alone efficiently edits nuclear DNA. Deamination is rapidly followed by excision of uracil residues and can lead to double-stranded breaks. It is not known to which protein networks these DNA mutators belong. Using a yeast two-hybrid screen, we identified the human homolog of Drosophila Tribbles 3, TRIB3, as an interactor for APOBEC3A and APOBEC3C. The interaction was confirmed by co-affinity purification. Co-transfection of APOBEC3A with a TRIB3 expression vector reduced nuclear DNA editing whereas siRNA knockdown of TRIB3 increased the levels of nuclear DNA editing, indicating that TRIB3 functioned as a repressor of A3A. It also repressed A3A-associated γH2AX positive double-stranded breaks. The interaction results in degradation of A3A in a proteasome-independent manner. TRIB3 has been linked to cancer and via its own interactors and links the A3A DNA mutators to the Rb-BRCA1-ATM network. TRIB3 emerges as an important guardian of genome integrity.
Complete list of metadata
Contributor : Jean-Pierre Vartanian Connect in order to contact the contributor
Submitted on : Monday, January 10, 2022 - 6:06:06 PM
Last modification on : Thursday, April 7, 2022 - 10:10:29 AM
Long-term archiving on: : Tuesday, April 12, 2022 - 12:46:28 AM


Publisher files allowed on an open archive


Distributed under a Creative Commons Attribution 4.0 International License




Marie-Ming Aynaud, Rodolphe Suspène, Pierre-Olivier Vidalain, Bianka Mussil, Denise Guétard, et al.. Human Tribbles 3 Protects Nuclear DNA from Cytidine Deamination by APOBEC3A. Journal of Biological Chemistry, 2012, 287 (46), pp.39182-39192. ⟨10.1074/jbc.M112.372722⟩. ⟨pasteur-03520008⟩



Record views


Files downloads