Other news

Publication : the role of p53 in DNA repair and the involvement in the Fanconi Anemia

Crédit : Sara Jaber/Institut Curie

p53 downregulates some DNA repair pathway. Latest discoveries of the team « Genetics of Tumor Suppression (CNRS, Institut Curie) » managed by Franck Toledo, University Pierre and Marie Curie Professor, recently published in Nature Communication should enable to better understanding  mecanisms at stake in the Fanconi Anemia.

p53 downregulates the Fanconi anaemia DNA repair pathway

Nat Commun. 2016 Apr 1;7:11091. doi: 10.1038/ncomms11091
Jaber S, Toufektchan E, Lejour V, Bardot B, Toledo F

« Germline mutations affecting telomere maintenance or DNA repair may, respectively, cause dyskeratosis congenita or Fanconi anaemia, two clinically related bone marrow failure syndromes. Mice expressing p53Δ31, a mutant p53 lacking the C terminus, model dyskeratosis congenita. Accordingly, the increased p53 activity in p53Δ31/Δ31 fibroblasts correlated with a decreased expression of 4 genes implicated in telomere syndromes. Here we show that these cells exhibit decreased mRNA levels for additional genes contributing to telomere metabolism, but also, surprisingly, for 12 genes mutated in Fanconi anaemia. Furthermore, p53Δ31/Δ31 fibroblasts exhibit a reduced capacity to repair DNA interstrand crosslinks, a typical feature of Fanconi anaemia cells. Importantly, the p53-dependent downregulation of Fanc genes is largely conserved in human cells. Defective DNA repair is known to activate p53, but our results indicate that, conversely, an increased p53 activity may attenuate the Fanconi anaemia DNA repair pathway, defining a positive regulatory feedback loop. »

Image © Sara Jaber/Institut Curie