Spt6 is a maintenance factor for centromeric CENP-A

Replication and transcription of genomic DNA requires partial disassembly of nucleosomes to allow progression of polymerases. This presents both an opportunity to remodel the underlying chromatin and a danger of losing epigenetic information. Centromeric transcription is required for stable incorporation of the centromere-specific histone dCENP-A in M/G1 phase, which depends on the eviction of previously deposited H3/H3.3-placeholder nucleosomes. Here we demonstrate that the histone chaperone and transcription elongation factor Spt6 spatially and temporarily coincides with centromeric transcription and prevents the loss of old CENP-A nucleosomes in both Drosophila and human cells. Spt6 binds directly to dCENP-A and dCENP-A mutants carrying phosphomimetic residues alleviate this association. Retention of phosphomimetic dCENP-A mutants is reduced relative to wildtype, while non-phosphorylatable dCENP-A retention is increased and accumulates at the centromere. We conclude that Spt6 acts as a conserved CENP-A maintenance factor that ensures long-term stability of epigenetic centromere identity during transcription-mediated chromatin remodeling

Transcription-replication conflicts: How they occur and how they are resolved

The frequent occurrence of transcription and DNA replication in cells results in many encounters, and thus conflicts, between the transcription and replication machineries. These conflicts constitute a major intrinsic source of genome instability, which is a hallmark of cancer cells. How the replication machinery progresses along a DNA molecule occupied by an RNA polymerase is an old question. Here we review recent data on the biological relevance of transcription-replication conflicts, and the factors and mechanisms that are involved in either preventing or resolving them, mainly in eukaryotes. On the basis of these data, we provide our current view of how transcription can generate obstacles to replication, including torsional stress and non-B DNA structures, and of the different cellular processes that have evolved to solve them

A key role for Ctf4 in coupling the MCM2-7 helicase to DNA polymerase α within the eukaryotic replisome

The eukaryotic replisome is a crucial determinant of genome stability, but its structure is still poorly understood. We found previously that many regulatory proteins assemble around the MCM2-7 helicase at yeast replication forks to form the replisome progression complex (RPC), which might link MCM2-7 to other replisome components. Here, we show that the RPC associates with DNA polymerase α that primes each Okazaki fragment during lagging strand synthesis. Our data indicate that a complex of the GINS and Ctf4 components of the RPC is crucial to couple MCM2-7 to DNA polymerase α. Others have found recently that the Mrc1 subunit of RPCs binds DNA polymerase epsilon, which synthesises the leading strand at DNA replication forks. We show that cells lacking both Ctf4 and Mrc1 experience chronic activation of the DNA damage checkpoint during chromosome replication and do not complete the cell cycle. These findings indicate that coupling MCM2-7 to replicative polymerases is an important feature of the regulation of chromosome replication in eukaryotes, and highlight a key role for Ctf4 in this process. © 2009 European Molecular Biology Organization | All Rights Reserved

Innovative methods for teaching molecular biology of the cell to medical students

Resumen del póster presentado al XL Congreso de la Sociedad Española de Bioquímica y Biología Molecular (SEBBM), celebrado en Barcelona del 23 al 26 de octubre de 2017.-- Vaqué, José P. et al.We are heading towards a new understanding of medicine where medical treatments will be personalized and precise. The knowledge and tools developed by biomedical research are essential for the success of this new medicine. To be able to offer in a near future diagnosis and treatment tailored to each patient, medical students need to understand the molecular processes involved in disease. The subject >Molecular Biology of the Cell> is essential to allow future doctors the implementation of this personalized medicine and to understand the mechanisms of action of drugs. The teaching experience in this particular subject as part of the Degree in Medicine at the University of Cantabria has showed us that some students are not motivated enough to understand the importance of Molecular Biology of the Cell for their future practice as medical doctors. We have introduced innovations into the teaching of this subject to increase student motivation. In addition, to improve student learning, we have used information and communication technologies (ICT) and other didactic methodologies to develop meaningful learning activities. We have incorporated educational trends such as BYOD (bring your own device) and Mobile Learning. Whereas teaching of Molecular Biology of the Cell requires still a teaching model in which the traditional university lecture plays a key role, we have introduced a new trend called Flipped Classroom to allow students to learn part of the key contents in the subject before attending the classroom, promoting an interactive environment. We present here the positive results that this new approach has achieved for medical students at the University of Cantabria.Peer Reviewe