The cullin Rtt101 promotes ubiquitin-dependent DNA-protein crosslink repair across the cell cycle.

DNA-protein crosslinks (DPCs) challenge faithful DNA replication and smooth passage of genomic information. Our study unveils the cullin E3 ubiquitin ligase Rtt101 as a DPC repair factor. Genetic analyses demonstrate that Rtt101 is essential for resistance to a wide range of DPC types including topoisomerase 1 crosslinks, in the same pathway as the ubiquitin-dependent aspartic protease Ddi1.

Cdc48/p97 segregase: Spotlight on DNA-protein crosslinks.

The ATP-dependent molecular chaperone Cdc48 (in yeast) and its human counterpart p97 (also known as VCP), are essential for a variety of cellular processes, including the removal of DNA-protein crosslinks (DPCs) from the DNA. Growing evidence demonstrates in the last years that Cdc48/p97 is pivotal in targeting ubiquitinated and SUMOylated substrates on chromatin, thereby supporting the DNA damage response. Along with its cofactors, notably Ufd1-Npl4, Cdc48/p97 has emerged as a central player in the unfolding and processing of DPCs.

SUMO in the regulation of DNA repair and transcription at nuclear pores.

Two related post-translational modifications, the covalent linkage of Ubiquitin and the Small Ubiquitin-related MOdifier (SUMO) to lysine residues, play key roles in the regulation of both DNA repair pathway choice and transcription. Whereas ubiquitination is generally associated with proteasome-mediated protein degradation, the impact of sumoylation has been more mysterious. In the cell nucleus, sumoylation effects are largely mediated by the relocalization of the modified targets, particularly in response to DNA damage.

Self-regulation of visual word form area activation with real-time fMRI neurofeedback.

The Visual Word Form Area (VWFA) is a key region of the brain's reading network and its activation has been shown to be strongly associated with reading skills. Here, for the first time, we investigated whether voluntary regulation of VWFA activation is feasible using real-time fMRI neurofeedback. 40 adults with typical reading skills were instructed to either upregulate (UP group, N = 20) or downregulate (DOWN group, N = 20) their own VWFA activation during six neurofeedback training runs.