FUNCTIONAL STUDIES OF NUSAP IN MICROTUBULE STABILITY, CHROMOSOME OSCILLATION AND MIDZONE FORMATION DURING MITOSIS

Abstract

DURING MITOSIS, AN ACCURATE SPINDLE FORMATION WITH A PRECISE CHROMOSOME ALIGNMENT IS THE PRE-CONDITIONS FOR PRECISE CHROMOSOME SEPARATION INTO TWO DAUGHTER CELLS AND THE PROCESS IS UNDER TIGHTLY CONTROL OF MICROTUBULE ASSOCIATED PROTEINS, MOTORS AND KINASES. NUSAP, A MICROTUBULE ASSOCIATED PROTEIN, PLAYS A CRITICAL ROLE IN STABILIZING MICROTUBULES BOTH IN VITRO AND IN VIVO. WE DISSECT THE FUNCTION OF NUSAP IN KINETOCHORE MICROTUBULES. OUR STUDY IDENTIFIES NUSAP AS A NOVEL NEGATIVE REGULATOR OF THE MICROTUBULE DEPOLYMERIZER-MCAK. MOREOVER, WE DEMONSTRATE THAT THE INTERACTION OF NUSAP WITH MCAK IS POSITIVELY MODULATED BY THE MITOTIC KINASE. OUR RESULTS ELUCIDATE A VITAL MECHANISM THAT NUSAP CONTROLS KINETOCHORE MICROTUBULE DYNAMICS BY MODULATING MCAK, IN AN AURORA B KINASE-DEPENDENT MANNER. FURTHERMORE, OUR FINDING SHOWS THAT NUSAP PIVOTALLY FUNCTIONS IN CHROMOSOME ALIGNMENT, ORIENTATION AND OSCILLATION THROUGH ITS REGULATION OF A CHROMOKINESIN?KID. FURTHERMORE, WE SPECIFICALLY INVESTIGA