title: The MRN-CtIP pathway is required for metaphase chromosome alignment.
abstract: Faithful duplication of the genome in S phase followed by its accurate segregation in mitosis is essential to maintain genomic integrity. Recent studies have suggested that proteins involved in DNA transactions are also required for whole-chromosome stability. Here we demonstrate that the MRN (Mre11, Rad50, and Nbs1) complex and CtIP are required for accurate chromosome segregation. Depletion of Mre11 or CtIP, antibody-mediated inhibition of Mre11, or small-molecule inhibition of MRN using mirin results in metaphase chromosome alignment defects in Xenopus egg extracts. Similarly, loss of MRN function adversely affects spindle assembly around DNA-coated beads in egg extracts. Inhibition of MRN function in mammalian cells triggers a metaphase delay and disrupts the RCC1-dependent RanGTP gradient. Addition of the Mre11 inhibitor mirin to egg extracts and mammalian cells reduces RCC1 association with mitotic chromosomes. Thus, the MRN-CtIP pathway contributes to Ran-dependent mitotic spindle assembly by modulating RCC1 chromosome association.
authors: Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, 630 W. 168(th) Street, New York, NY 10032, USA.
authors: Lorene
authors: L
authors: Rozier
authors: Yige
authors: Y
authors: Guo
authors: Shaun
authors: S
authors: Peterson
authors: Mai
authors: M
authors: Sato
authors: Richard
authors: R
authors: Baer
authors: Jean
authors: J
authors: Gautier
authors: Yinghui
authors: Y
authors: Mao
mesh_terms: D017766:Acid Anhydride Hydrolases; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology; D002457:Cell Extracts; D020090:Chromosome Segregation; D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology; D004706:Endodeoxyribonucleases; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D000076228:MRE11 Homologue Protein; D008677:Metaphase; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008938:Mitosis; D046912:Multiprotein Complexes / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D059010:Single-Cell Analysis; D008941:Spindle Apparatus / Q000378:metabolism*; D014981:Xenopus; D029867:Xenopus Proteins / Q000502:physiology; D020931:ran GTP-Binding Protein / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002457:Cell Extracts; D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; C121766:MRE11 protein, human; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes; C112156:NBN protein, human; D009687:Nuclear Proteins; C120587:RAN protein, human; C062521:RCC1 protein, human; C122167:TPX2 protein, human; D029867:Xenopus Proteins; D004706:Endodeoxyribonucleases; D000076228:MRE11 Homologue Protein; C410741:RBBP8 protein, human; D017766:Acid Anhydride Hydrolases; C112158:RAD50 protein, human; D020931:ran GTP-Binding Protein; D045643:DNA Repair Enzymes