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A mitosis-specific and R loop-driven ATR pathway promotes faithful chromosome segregation.

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  • المؤلفون: Kabeche L;Kabeche L; Nguyen HD; Nguyen HD; Buisson R; Buisson R; Zou L; Zou L; Zou L
  • المصدر:
    Science (New York, N.Y.) [Science] 2018 Jan 05; Vol. 359 (6371), pp. 108-114. Date of Electronic Publication: 2017 Nov 23.
  • نوع النشر :
    Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • اللغة:
    English
  • معلومة اضافية
    • المصدر:
      Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 0404511 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-9203 (Electronic) Linking ISSN: 00368075 NLM ISO Abbreviation: Science Subsets: MEDLINE
    • بيانات النشر:
      Publication: : Washington, DC : American Association for the Advancement of Science
      Original Publication: New York, N.Y. : [s.n.] 1880-
    • الموضوع:
      Centromere/*enzymology ; Chromosome Segregation/*genetics ; Mitosis/*genetics; Ataxia Telangiectasia Mutated Proteins/genetics ; Ataxia Telangiectasia Mutated Proteins/metabolism ; Aurora Kinase A/metabolism ; Cell Line, Tumor ; Checkpoint Kinase 1/metabolism ; Chromosomal Proteins, Non-Histone/metabolism ; Humans ; Microfilament Proteins/metabolism
    • نبذة مختصرة :
      The ataxia telangiectasia mutated and Rad3-related (ATR) kinase is crucial for DNA damage and replication stress responses. Here, we describe an unexpected role of ATR in mitosis. Acute inhibition or degradation of ATR in mitosis induces whole-chromosome missegregation. The effect of ATR ablation is not due to altered cyclin-dependent kinase 1 (CDK1) activity, DNA damage responses, or unscheduled DNA synthesis but to loss of an ATR function at centromeres. In mitosis, ATR localizes to centromeres through Aurora A-regulated association with centromere protein F (CENP-F), allowing ATR to engage replication protein A (RPA)-coated centromeric R loops. As ATR is activated at centromeres, it stimulates Aurora B through Chk1, preventing formation of lagging chromosomes. Thus, a mitosis-specific and R loop-driven ATR pathway acts at centromeres to promote faithful chromosome segregation, revealing functions of R loops and ATR in suppressing chromosome instability.
      (Copyright © 2018, American Association for the Advancement of Science.)
    • Comments:
      Comment in: Science. 2018 Jan 5;359(6371):30-31. doi: 10.1126/science.aar4799. (PMID: 29302000)
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    • Grant Information:
      R00 CA212154 United States CA NCI NIH HHS; K99 CA212154 United States CA NCI NIH HHS; T32 CA009216 United States CA NCI NIH HHS; R01 GM076388 United States GM NIGMS NIH HHS; R01 CA197779 United States CA NCI NIH HHS; T32 DK007540 United States DK NIDDK NIH HHS
    • الرقم المعرف:
      0 (Chromosomal Proteins, Non-Histone)
      0 (Microfilament Proteins)
      0 (centromere protein F)
      EC 2.7.11.1 (ATR protein, human)
      EC 2.7.11.1 (AURKA protein, human)
      EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins)
      EC 2.7.11.1 (Aurora Kinase A)
      EC 2.7.11.1 (CHEK1 protein, human)
      EC 2.7.11.1 (Checkpoint Kinase 1)
    • الموضوع:
      Date Created: 20171125 Date Completed: 20180410 Latest Revision: 20190731
    • الموضوع:
      20250114
    • الرقم المعرف:
      PMC5875943
    • الرقم المعرف:
      10.1126/science.aan6490
    • الرقم المعرف:
      29170278