PP18. THE GENETICS OF PREMATURE CENTROMERE SEPARATION SYNDROMES
BAJIC VLADAN1, Potparevic-Spremo Biljana2, Djelic Ninoslav3 and Lada Zivkovic2 1. Institute for Biomedical Research, Galenika a.d., Serbia and Montenegro 2. Department of Biology, Faculty of Pharmacy, University of Belgrade, 3. Department of Biology, Faculty of Veterinary Medicine, University of Belgrade, Serbia and Montenegro e-mail: vladanpfd@eunet.yu
*Corresponding Author:
page: 55

Abstract

Premature separation syndromes strongly support evidence that spatial and temporal organization of the cell cycle is crucial for maintaining genomic stability. Premature centromere separation is associated with various diseases, chromosomal instability syndromes, old age, Alzheimer's and tumors. The sequence of centromere separation is genetically controlled. PCS was first described in individuals with Roberts's syndrome, on all chromosomes within one mitosis and results in numerous abnormalities during prenatal and postnatal development. Still, PCS can be found in a high frequency rate (5% or more) as a sole chromosome abnormality in individuals with no recognizable clinical manifestation. Still, these Individuals with PCD were found to have altered kinetics of the cell cycle. In order to fully elucidate the problem we used an alpha-satellite cetromeric probe (FISH) to find the exact time of PCS induction in the cell cycle in normal young individuals, normal ol der subjects and Alzheimer's. PCS in young normal individuals was induced by using a protein inhibitor Cycloheximide. Peripheral blood lymphocytes were cytogenetically prepared for FISH analysis. Our results show that PCS was induced very early in the cell cycle, i.e. in the interphase (G2-phase) of the cell cycle in all experimental groups and the Cycloheximide exposed group. Early induction of PCS in our experiment by Cycloheximide shows that the origin of the defects are based in the centromere. Protein synthesis is a prerequisite for centromere assembly and cohesion. We can conclude that the centromere is a functional organized region of the chromosome with a fundamental role in mitotic spindle checkpoint organization and at least 6 genes have been involved with such a checkpoint showing that the origin of PCS is genetically heterogeneous.




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