Genome stability is guarded by yeast Rtt105 through multiple mechanisms.

Ty1 mobile DNA element is the most abundant and mutagenic retrotransposon present in the genome of the budding yeast Saccharomyces cerevisiae. Protein regulator of Ty1 transposition 105 (Rtt105) associates with large subunit of RPA and facilitates its loading onto a single-stranded DNA at replication forks. Here, we dissect the role of RTT105 in the maintenance of genome stability under normal conditions and upon various replication stresses through multiple genetic analyses. RTT105 is essential for viability in cells experiencing replication problems and in cells lacking functional S-phase checkpoints and DNA repair pathways involving homologous recombination. Our genetic analyses also indicate that RTT105 is crucial when cohesion is affected and is required for the establishment of normal heterochromatic structures. Moreover, RTT105 plays a role in telomere maintenance as its function is important for the telomere elongation phenotype resulting from the Est1 tethering to telomeres. Genetic analyses indicate that rtt105Δ affects the growth of several rfa1 mutants but does not aggravate their telomere length defects. Analysis of the phenotypes of rtt105Δ cells expressing NLS-Rfa1 fusion protein reveals that RTT105 safeguards genome stability through its role in RPA nuclear import but also by directly affecting RPA function in genome stability maintenance during replication.

Cytokine and chemokine regulation of venous thromboembolism.

Morbidity and mortality from venous thromboembolism (VTE), which refers to deep vein thrombosis and pulmonary embolism, have a substantial effect on the global burden of disease. The field of venous thrombosis research has been dramatically changed over the past 10 years with the improvement of animal models that shed some light on the interaction between inflammation and thrombosis. Important recent advances provided evidence of the implication of the innate immune system in venous thrombosis. In this review, we highlighted the cytokines and chemokines that regulate mechanisms of thrombus formation and resolution. Cytokines are pleiotropic, redundant, and multifunctional endogenous mediators orchestrating the inflammatory responses leading to thrombus formation or resolution. The use of experimental models has revealed the pro-thrombotic activity of some cytokines including interferon-γ, interleukin (IL)-6, chemokine ligand 2, IL-17A, IL-9, IL-1ß, and transforming growth factor-ß. Other cytokines such as IL-10, tumor necrosis factor-α, and IL-8 appear to promote thrombus resolution in late phase of venous thromboembolism. The purpose of this review is to bring together the current knowledge regarding the cytokines and chemokines that have been involved in thrombosis formation and resolution. We postulate that an imbalance between pro-thrombotic and anti-thrombotic cytokines/chemokines may be involved in the pathophysiology of VTE. However, in-depth basic and clinical research in venous thrombosis is still require to fully understand the precise mechanism of action of these cytokines.