FACT Assists Base Excision Repair by Boosting the Remodeling Activity of RSC

John Lalith Charles Richard (1, 2, 3) , Manu Shubhdarshan Shukla (1, 2, 3) , Hervé Menoni (2, 3) , Khalid Ouararhni (4) , Imtiaz Nisar Lone (2, 3) , Yohan Roulland (1) , Christophe Papin (4) , Elsa Ben Simon (2, 3) , Tapas Kundu (5) , Ali Hamiche (4) , Dimitar Angelov (2, 3) , Stefan Dimitrov (1)

1 INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble
2 LBMC UMR 5239 - Laboratoire de biologie et modélisation de la cellule
3 INMG - Institut NeuroMyoGène
4 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
5 Transcription and Disease Laboratory [Bangalore, Inde]

FACT, in addition to its role in transcription, is likely implicated in both transcription-coupled nucleotide excision repair and DNA double strand break repair. Here, we present evidence that FACT could be directly involved in Base Excision Repair and elucidate the chromatin remodeling mechanisms of FACT during BER. We found that, upon oxidative stress, FACT is released from transcription related protein complexes to get associated with repair proteins and chromatin remodelers from the SWI/SNF family. We also showed the rapid recruitment of FACT to the site of damage, coincident with the glycosylase OGG1, upon the local generation of oxidized DNA. Interestingly, FACT facilitates uracil-DNA glycosylase in the removal of uracil from nucleosomal DNA thanks to an enhancement in the remodeling activity of RSC. This discloses a novel property of FACT wherein it has a co-remodeling activity and strongly enhances the remodeling capacity of the chromatin remodelers. Altogether, our data suggest that FACT may acts in concert with RSC to facilitate excision of DNA lesions during the initial step of BER.

Domains: Biochemistry, Molecular Biology

John Lalith Charles Richard, Manu Shubhdarshan Shukla, Hervé Menoni, Khalid Ouararhni, Imtiaz Nisar Lone, et al.. FACT Assists Base Excision Repair by Boosting the Remodeling Activity of RSC. PLoS Genetics, 2016, 12 (7), pp.e1006221. ⟨10.1371/journal.pgen.1006221⟩. ⟨inserm-02163206⟩