Sister Chromatid Cohesion, Chromosome Instability (CIN) and Diseases

Abstract

AbstractTo pass on the complete set of genetic information from mother to daughter cells in mitosis, or from parental germ cells to gametes in meiosis, chromosomal deoxyribonucleic acid (DNA) must be accurately replicated and sister chromatids must be held together before they separate in anaphase. Sister chromatid cohesion is a dynamic process that is regulated by the cohesin complex, cell cycle regulation of cohesin ring loading, cohesion establishment, maintenance and dissolution. Cohesion‐related proteins also play additional roles in DNA replication, DNA repair, and gene regulation. Defects in sister chromatid cohesion or cohesion dissolution will lead to aneuploidy and chromosome instability (CIN). Mutations or misregulation of cohesin subunits, or cohesion‐related genes have been implicated in cancers, cohesinopathies, neurological diseases and aneuploid oocytes observed in maternal ageing. Understanding of the pathology of these diseases enables recent development of cohesion genes as biomarkers in prognosis and therapies that target cohesion defects or CIN.Key ConceptsSister chromatid cohesion is an important cell cycle‐regulated process that maintains chromosome stability.Sister chromatid cohesion is established in S phase coupled with DNA replication, maintained in G2/M phase until anaphase onset.Many cohesion‐related proteins also play roles in DNA replication, DNA repair and gene regulation.Mutations or misregulation of cohesin subunits, or cohesion‐related genes have been implicated in cancers, cohesinopathies, neurological diseases and aneuploid oocytes observed in maternal ageing.Cohesion genes can be used as biomarkers in cancer prognosis, and cancer therapies can target tumours with cohesion defects or CIN.