Mary L. Hixon ¹ and Antonio Gualberto ^1,2

1Division of Cardiovascular Research, Department of Medicine, St. Elizabeth's Medical Center, Boston, MA 02135, USA, ²Department of Cardiovascular and Metabolic Diseases, Pfizer Central Research Division, Eastern Point Rd., Groton, CT 06340

TABLE OF CONTENTS

1. Abstract

2. Introduction

3. Discussion:

3.1. Chromatid cohesion

3.1.1. Separin, Securin and the onset of anaphase

3.2.The Anaphase Promoting Complex

3.2.1. The Control of APC/C activity

3.3. The mitotic spindle cell cycle checkpoint

4. Perspectives

5. Acknowledgements

6. References

1. ABSTRACT

A precise coordination of multiple cell cycle events is required to ensure proper mitosis. Chromosome cohesion must be maintained until all chromosomes are attached to opposite poles of the mitotic spindle and aligned at the metaphase plate. At the onset of anaphase, the activity of separins contributes to the release of cohesins from chromosomes, allowing for the segregation of bivalents to opposite spindle poles. Separin activity is blocked by binding to a class of proteins known as securins, whose turnover at the metaphase-to-anaphase transition is triggered by the Anaphase Promoting Complex or cyclosome. The mitotic spindle cell cycle checkpoint coordinates the timing of these events and acts as input mechanism for DNA damage/stress pathways. Failure of this precise network leads to genomic instability and/or cell death.