Sic1-induced DNA rereplication during meiosis

Orderly progression through meiosis requires strict regulation of DNA metabolic events, so that a single round of DNA replication is systematically followed by a recombination phase and 2 rounds of chromosome segregation. We report here the disruption of this sequence of events in Saccharomyces cerevisiae through meiosis-specific induction of the cyclin-dependent kinase (CDK) inhibitor Sic1 mutated at multiple phosphorylation sites. Accumulation of this stabilized version of Sic1 led to significant DNA rereplication in the absence of normal chromosome segregation. Deletion of DMC1 abolished DNA rereplication, but additional deletion of RAD17 restored the original phenotype. Therefore, activation of the meiotic recombination checkpoint, which arrests meiotic progression at pachytene, suppressed DNA rereplication resulting from Sic1 stabilization. In contrast to deletion of DMC1, deletion of NDT80, which encodes a transcription factor required for pachytene exit, did not inhibit DNA rereplication. Our results provide strong evidence that CDK activity is required to prevent inappropriate initiation of DNA synthesis before the meiotic divisions

A Link between Aurora Kinase and Clp1/Cdc14 Regulation Uncovered by the Identification of a Fission Yeast Borealin-Like Protein

The chromosomal passenger complex (CPC) regulates various events in cell division. This complex is composed of a catalytic subunit, Aurora B kinase, and three nonenzymatic subunits, INCENP, Survivin, and Borealin. Together, these four subunits interdependently regulate CPC function, and they are highly conserved among eukaryotes. However, a Borealin homologue has never been characterized in the fission yeast, Schizosaccharomyces pombe. Here, we isolate a previously uncharacterized S. pombe protein through association with the Cdc14 phosphatase homologue, Clp1/Flp1, and identify it as a Borealin-like member of the CPC. Nbl1 (novel Borealin-like 1) physically associates with known CPC components, affects the kinase activity and stability of the S. pombe Aurora B homologue, Ark1, colocalizes with known CPC subunits during mitosis, and shows sequence similarity to human Borealin. Further analysis of the Clp1–Nbl1 interaction indicates that Clp1 requires CPC activity for proper accumulation at the contractile ring (CR). Consistent with this, we describe negative genetic interactions between mutant alleles of CPC and CR components. Thus, this study characterizes a fission yeast Borealin homologue and reveals a previously unrecognized connection between the CPC and the process of cytokinesis in S. pombe

Building a Clinical Research Network in Trauma Orthopaedics: The Major Extremity Trauma Research Consortium (METRC)

OBJECTIVESLessons learned from battle have been fundamental to advancing the care of injuries that occur in civilian life. Equally important is the need to further refine these advances in civilian practice, so they are available during future conflicts. The Major Extremity Trauma Research Consortium (METRC) was established to address these needs.METHODSMETRC is a network of 22 core level I civilian trauma centers and 4 core military treatment centers-with the ability to expand patient recruitment to more than 30 additional satellite trauma centers for the purpose of conducting multicenter research studies relevant to the treatment and outcomes of orthopaedic trauma sustained in the military. Early measures of success of the Consortium pertain to building of an infrastructure to support the network, managing the regulatory process, and enrolling and following patients in multiple studies.RESULTSMETRC has been successful in maintaining the engagement of several leading, high volume, level I trauma centers that form the core of METRC; together they operatively manage 15,432 major fractures annually. METRC is currently funded to conduct 18 prospective studies that address 6 priority areas. The design and implementation of these studies are managed through a single coordinating center. As of December 1, 2015, a total of 4560 participants have been enrolled.CONCLUSIONSSuccess of METRC to date confirms the potential for civilian and military trauma centers to collaborate on critical research issues and leverage the strength that comes from engaging patients and providers from across multiple centers