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Prix René et Andrée Duquesne 2015 Ligue contre le cancer : Hinrich GRONEMEYER Médaille de bronze 2015 CNRS : Evi SOUTOGLOU Médaille de cristal 2015 CNRS : Philippe ANDRE
Figure (A) When retinoic acid (ATRA) is not available to activate the RAR / RXR nuclear receptor heterodimers, SALL4A expression is off. Under these conditions, the transcription repressor ZBTB16 binds to the KIT gene promoter, blocking the access to SOHLH1 transcription factor and preventing expression of KIT. Spermatogonia (ZBTB16-positive, in red) remain "undifferentiated" (KIT-negative, in green). (B) In the presence of ATRA (yellow triangle), RAR / RXR heterodimers located on the Sall4a gene promoter are activated. They induce the production of SALL4A, which has the ability to interact with ZBTB16 and drives it away from the promoter of KIT gene, enabling the action of SOHLH1 and therefore KIT expression. Spermatogonia (ZBTB16-positive, in red) switch to the "differentiated" state (KIT-positive, in green).
Oct. 1, 2015
The team of Norbert B. Ghyselinck and Manuel Mark has discovered one of the mechanisms by which the active metabolite of vitamin A, retinoic acid (ATRA), controls the expression of KIT, a membrane receptor essential for differentiation of germ cells and the expression of which is often dysregulated in testicular cancers. The researchers further demonstrate that germ cells devoid of ATRA nuclear receptors normally progress through meiosis and differentiate into spermatozoa. This unexpected discovery means that the action of ATRA on meiosis is of paracrine nature. This study is published on October 1st in the journal PLoS Genetics.
While being dispensable for somatic hypermutation (SHM), the DNA repair factor Parp3 plays a dual role during immunoglobulin class switch recombination (CSR). Parp3 promotes the repair of double stranded DNA breaks (DSBs) induced by AID through the non homologous end joining (NHEJ) pathway and protects the immunoglobulin heavy (IgH) chain locus from sustained AID-induced DNA damage by promoting the eviction of the mutagenic enzymatic activity of AID from chromatin.
June 15, 2015
The team of Bernardo Reina-San-Martin at IGBMC revealed new control mechanisms operating during antibody diversification. They have shown that the DNA repair factor Parp3 plays a dual role during immunoglobulin class switch recombination (CSR).
Parp3 promotes the repair of physiological DNA double strand breaks inflicted at the immunoglobulin heavy chain (IgH) locus and it protects the locus against sustained DNA damage.
This work provides novel insight in the mechanisms underlying the efficient generation of protective antibodies and the maintenance of genomic stability.
These results are published in Plos Genetics May 22nd 2015.