title: Structure-specific endonucleases: guardians of fragile site stability.
abstract: Fragile sites are conserved loci predisposed to form breaks in metaphase chromosomes. The inherent instability of these loci is associated with chromosomal rearrangements in cancers and is a feature of cells from patients with chromosomal instability syndromes. One class of fragile sites, the common fragile sites (CFSs), have previously been shown to recruit several DNA repair proteins after the completion of bulk DNA synthesis in the cell, probably indicative of their inability to complete timely DNA replication. CFS loci are also prone to trigger mitotic non-disjunction of sister chromatids, leading to the formation of ultra-fine anaphase bridges (UFBs) and micronuclei. We discuss recent developments in the CFS field; in particular, the role of DNA structure-specific endonucleases in promoting cleavage at CFSs.
authors.affiliation: Nordea Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Denmark.
authors.forename: Sheroy
authors.initials: S
authors.lastname: Minocherhomji
authors.affiliation: Nordea Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Denmark. Electronic address: iandh@sund.ku.dk.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Hickson
mesh_terms: D000818:Animals; D043283:Chromosome Fragile Sites; D004260:DNA Repair; D049914:DNA Repair-Deficiency Disorders / Q000235:genetics; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000502:physiology*; D004706:Endodeoxyribonucleases / Q000502:physiology*; D004720:Endonucleases / Q000502:physiology*; D015870:Gene Expression; D042822:Genomic Instability; D006801:Humans
chemical_list: D004268:DNA-Binding Proteins; C507947:Eme1 protein, human; D004706:Endodeoxyribonucleases; D004720:Endonucleases; C498772:MUS81 protein, human
keywords: MUS81–EME1; common fragile sites; fragile site expression; structure-specific endonucleases