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Purpose of review To review the evidence about video game-based therapeutic intervention for people diagnosed with depressive disorders. Recent findings Psychotherapy has been proved to reduce depressive symptoms and is a key element in the treatment of depressive disorders. However, geographical, economical and stigmatized concerns are barriers to access to psychotherapy. New technologies and videos games can overcome some of these barriers by providing teleconferencing evidence-based therapy as time as they may offer an interactive entertainment. Summary Overall, video game-based interventions were useful and effective in reducing symptoms of depressive disorders. Seven of the studies were published in the last 5 years, which reflects the increased research interest in video game-based interventions for depression. Overall, when adherence was reported, rates of acceptability and feasibility were high.

The advance and stability of replication forks rely on a tight co-regulation of the processes of DNA synthesis and nucleosome assembly. We have addressed the relevance of parental histone recycling in the mechanisms of DNA damage tolerance (DDT) – homologous recombination (HR) and translesion synthesis (TLS) – that assist replication forks under conditions that block their advance. We show that mutants affected in the deposition of parental histones are impaired in the recombinational repair of the single-strand DNA gaps generated during DDT, with the defects being more severe in mutants impaired in the lagging strand-specific deposition pathway. These recombinational defects are not due to a deficit of parental histones at the nascent strands but to an excess of parental nucleosomes at the invaded strand that destabilizes the sister chromatid junction formed after strand invasion. In conclusion, parental histone distribution at stressed forks regulates HR and provides a potential mechanism for the choice between HR and TLS that would depend on whether DNA synthesis is blocked at the lagging or the leading strand.

Cdc7 and its regulator Dbf4 (Dbf4-dependent kinase; DDK) form an essential complex due to its function in replication initiation, which is carried out by phosphorylating different residues at the helicase MCM during the G1/S transition. In response to replication stress, late origins are inhibited to prevent cell cycle progression until the problems are resolved. In yeast, this inhibition is partially achieved by attenuating DDK activity. In addition, evidence from yeast to human shows that Cdc7 is required for a successful DNA damage response by coordinating multiple processes dealing with replication stress (replication checkpoint, DNA damage tolerance and break-induced replication) through mechanisms that go beyond its role in origin activation. These studies reveal the importance of getting a better understanding of the spatiotemporal regulation of DDK. Here, we will discuss how DDK operates in these processes and its putative role in controlling the activity of replication and repair factors at specific nuclease-resistant nucleoprotein scaffolds.

The minichromosome maintenance (MCM) helicase physically interacts with the recombination proteins Rad51 and Rad52 from yeast to human cells. We show, in Saccharomyces cerevisiae, that these interactions occur within a nuclease-insoluble scaffold enriched in replication/repair factors. Rad51 accumulates in a MCM- and DNA-binding-independent manner and interacts with MCM helicases located outside of the replication origins and forks. MCM, Rad51, and Rad52 accumulate in this scaffold in G1 and are released during the S phase. In the presence of replication-blocking lesions, Cdc7 prevents their release from the scaffold, thus maintaining the interactions. We identify a rad51 mutant that is impaired in its ability to bind to MCM but not to the scaffold. This mutant is proficient in recombination but partially defective in single-stranded DNA (ssDNA) gap filling and replication fork progression through damaged DNA. Therefore, cells accumulate MCM/Rad51/Rad52 complexes at specific nuclear scaffolds in G1 to assist stressed forks through non-recombinogenic functions., This work was supported by grants BFU2015-63698-P and PGC2018-099182-B-I00 (to F.P.) from the Spanish government, and project-ID 393547839-SFB1361 (to H.D.U.) from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation). M.J.C.-L., M.I.C.-L., C.G.-G, A.Y.-V., and R.G.-P were recipients of pre-doctoral training grants from the Spanish government.