title: Securin is not required for chromosomal stability in human cells.
abstract: Abnormalities of chromosome number are frequently observed in cancers. The mechanisms regulating chromosome segregation in human cells are therefore of great interest. Recently it has been reported that human cells without an hSecurin gene lose chromosomes at a high frequency. Here we show that, after hSecurin knockout through homologous recombination, chromosome losses are only a short, transient effect. After a few passages hSecurin(-/-) cells became chromosomally stable and executed mitoses normally. This was unexpected, as the securin loss resulted in a persisting reduction of the sister-separating protease separase and inefficient cleavage of the cohesin subunit Scc1. Our data demonstrate that securin is dispensable for chromosomal stability in human cells. We propose that human cells possess efficient mechanisms to compensate for the loss of genes involved in chromosome segregation.
authors.affiliation: Institute of Human Genetics, Technical University Munich, Munich, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Pfleghaar
authors.forename: Simone
authors.initials: S
authors.lastname: Heubes
authors.forename: Jürgen
authors.initials: J
authors.lastname: Cox
authors.forename: Olaf
authors.initials: O
authors.lastname: Stemmann
authors.forename: Michael R
authors.initials: MR
authors.lastname: Speicher
mesh_terms: D000705:Anaphase; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D043171:Chromosomal Instability / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009363:Neoplasm Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D064249:Securin; D064247:Separase
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C490529:MCD1 protein, S cerevisiae; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D029701:Saccharomyces cerevisiae Proteins; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human; D010450:Endopeptidases; C577986:ESP1 protein, S cerevisiae; C577987:ESPL1 protein, human; D064247:Separase