کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2035237 | 1072152 | 2014 | 15 صفحه PDF | دانلود رایگان |
• Polo-like kinase 1 (Plk1) is required for CENP-A deposition in human cells
• Plk1 phosphorylates the Mis18 complex to promote its localization
• Cyclin-dependent kinase (CDK) inhibits Mis18 complex assembly
• Bypassing Plk1 and CDK regulation causes constitutive CENP-A deposition
SummaryTo ensure the stable transmission of the genome during vertebrate cell division, the mitotic spindle must attach to a single locus on each chromosome, termed the centromere. The fundamental requirement for faithful centromere inheritance is the controlled deposition of the centromere-specifying histone, CENP-A. However, the regulatory mechanisms that ensure the precise control of CENP-A deposition have proven elusive. Here, we identify polo-like kinase 1 (Plk1) as a centromere-localized regulator required to initiate CENP-A deposition in human cells. We demonstrate that faithful CENP-A deposition requires integrated signals from Plk1 and cyclin-dependent kinase (CDK), with Plk1 promoting the localization of the key CENP-A deposition factor, the Mis18 complex, and CDK inhibiting Mis18 complex assembly. By bypassing these regulated steps, we uncoupled CENP-A deposition from cell-cycle progression, resulting in mitotic defects. Thus, CENP-A deposition is controlled by a two-step regulatory paradigm comprised of Plk1 and CDK that is crucial for genomic integrity.
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Journal: - Volume 158, Issue 2, 17 July 2014, Pages 397–411