Separase and Roads to Disengage Sister Chromatids during Anaphase.

Receiving complete and undamaged genetic information is vital for the survival of daughter cells after chromosome segregation. The most critical steps in this process are accurate DNA replication during S phase and a faithful chromosome segregation during anaphase. Any errors in DNA replication or chromosome segregation have dire consequences, since cells arising after division might have either changed or incomplete genetic information. Accurate chromosome segregation during anaphase requires a protein complex called cohesin, which holds together sister chromatids. This complex unifies sister chromatids from their synthesis during S phase, until separation in anaphase. Upon entry into mitosis, the spindle apparatus is assembled, which eventually engages kinetochores of all chromosomes. Additionally, when kinetochores of sister chromatids assume amphitelic attachment to the spindle microtubules, cells are finally ready for the separation of sister chromatids. This is achieved by the enzymatic cleavage of cohesin subunits Scc1 or Rec8 by an enzyme called Separase. After cohesin cleavage, sister chromatids remain attached to the spindle apparatus and their poleward movement on the spindle is initiated. The removal of cohesion between sister chromatids is an irreversible step and therefore it must be synchronized with assembly of the spindle apparatus, since precocious separation of sister chromatids might lead into aneuploidy and tumorigenesis. In this review, we focus on recent discoveries concerning the regulation of Separase activity during the cell cycle.

Contribution of MAML1 in esophageal squamous cell carcinoma tumorigenesis.

BACKGROUND: Notch signaling pathway is involved in different cellular and developmental processes including cell proliferation, differentiation and apoptosis. Mastermind like1 (MAML1) is a critical key transcription coactivator of this pathway. In this study, we aimed to examine MAML1 protein expression in esophageal squamous cell carcinoma (ESCC) and reveal its association with clinicopathological variables of the patients. METHODS: Tumoral and their margin normal tissues from 56 ESCC patients were recruited for protein expression analysis using immunohistochemistry (IHC). Furthermore, MAML1 expression was analyzed in ESCC cell line KYSE-30 using immunocytochemistry. RESULTS: Overexpression of MAML1 was detected in 59% of tumor samples. It was significantly associated with different indices of poor prognosis including depth of tumor invasion (P=0.026), grade of tumor differentiation (P=0.002), stage of tumor progression (P=0.004) and sex (P=0.027). CONCLUSION: Beside the appearing evidences explaining MAML1 role in different cellular processes and its deviations in different malignancies and also based on its correlation with different clinicopathological variables of ESCC, MAML1 can be proposed as potentially novel molecular marker for ESCC progression and tumorigenesis as well as therapeutic target to inhibit and reverse progression and development of the disease.