title: Defective decatenation checkpoint function is a common feature of melanoma.
abstract: A hallmark of cancer is genomic instability that is considered to provide the adaptive capacity of cancers to thrive under conditions in which the normal precursors would not survive. Recent genomic analysis has revealed a very high degree of genomic instability in melanomas, although the mechanism by which this instability arises is not known. Here we report that a high proportion (68%) of melanoma cell lines are either partially (40%) or severely (28%) compromised for the G2 phase decatenation checkpoint that normally functions to ensure that the sister chromatids are able to separate correctly during mitosis. The consequence of this loss of checkpoint function is a severely reduced ability to partition the replicated genome in mitosis and thereby increase genomic instability. We also demonstrate that decatenation is dependent on both TopoIIα and β isoforms. The high incidence of decatenation checkpoint defect is likely to be a major contributor to the high level of genomic instability found in melanomas.
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia.
authors.forename: Kelly
authors.initials: K
authors.lastname: Brooks
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia.
authors.forename: Kee Ming
authors.initials: KM
authors.lastname: Chia
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia.
authors.forename: Loredana
authors.initials: L
authors.lastname: Spoerri
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia.
authors.forename: Pamela
authors.initials: P
authors.lastname: Mukhopadhyay
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia.
authors.forename: Matthew
authors.initials: M
authors.lastname: Wigan
authors.affiliation: Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Stark
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia.
authors.forename: Sandra
authors.initials: S
authors.lastname: Pavey
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia. Electronic address: brianG@uq.edu.au.
authors.forename: Brian
authors.initials: B
authors.lastname: Gabrielli
mesh_terms: D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D004250:DNA Topoisomerases, Type II / Q000235:genetics; D016195:G2 Phase / Q000235:genetics; D018816:Genes, cdc / Q000235:genetics*; D042822:Genomic Instability / Q000235:genetics*; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D008938:Mitosis / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D012854:Sister Chromatid Exchange / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D034741:RNA, Small Interfering; D004250:DNA Topoisomerases, Type II