Somatic hypermutation of human mitochondrial and nuclear DNA by APOBEC3 cytidine deaminases, a pathway for DNA catabolism. - Institut Pasteur Accéder directement au contenu
Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2011

Somatic hypermutation of human mitochondrial and nuclear DNA by APOBEC3 cytidine deaminases, a pathway for DNA catabolism.

Résumé

The human APOBEC3 (A3A-A3H) locus encodes six cytidine deaminases that edit single-stranded DNA, the result being DNA peppered with uridine. Although several cytidine deaminases are clearly restriction factors for retroviruses and hepadnaviruses, it is not known if APOBEC3 enzymes have roles outside of these settings. It is shown here that both human mitochondrial and nuclear DNA are vulnerable to somatic hypermutation by A3 deaminases, with APOBEC3A standing out among them. The degree of editing is much greater in patients lacking the uracil DNA-glycolyase gene, indicating that the observed levels of editing reflect a dynamic composed of A3 editing and DNA catabolism involving uracil DNA-glycolyase. Nonetheless, hyper- and lightly mutated sequences went hand in hand, raising the hypothesis that recurrent low-level mutation by APOBEC3A could catalyze the transition from a healthy to a cancer genome.

Dates et versions

pasteur-00591073 , version 1 (06-05-2011)

Identifiants

Citer

Rodolphe Suspène, Marie-Ming Aynaud, Denise Guétard, Michel Henry, Grace Eckhoff, et al.. Somatic hypermutation of human mitochondrial and nuclear DNA by APOBEC3 cytidine deaminases, a pathway for DNA catabolism.. Proceedings of the National Academy of Sciences of the United States of America, 2011, 108 (12), pp.4858-63. ⟨10.1073/pnas.1009687108⟩. ⟨pasteur-00591073⟩

Collections

PASTEUR CNRS
33 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More