Your browser doesn't support javascript.
loading
Centromeric chromatin integrity is compromised by loss of Cdk5rap2, a transcriptional activator of CENP-A.
Wang, Xidi; Rosales, Jesusa L; Gao, Xu; Lee, Ki-Young.
Afiliación
  • Wang X; Department of Biochemistry & Molecular Biology, Harbin Medical University, Harbin, China; Department of Cell Biology & Anatomy, Arnie Charbonneau Cancer and Alberta Children's Hospital Research Institutes, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
  • Rosales JL; Department of Cell Biology & Anatomy, Arnie Charbonneau Cancer and Alberta Children's Hospital Research Institutes, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
  • Gao X; Department of Biochemistry & Molecular Biology, Harbin Medical University, Harbin, China. Electronic address: gaoxu6712@163.com.
  • Lee KY; Department of Cell Biology & Anatomy, Arnie Charbonneau Cancer and Alberta Children's Hospital Research Institutes, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. Electronic address: kylee@ucalgary.ca.
Biomed Pharmacother ; 138: 111463, 2021 Jun.
Article en En | MEDLINE | ID: mdl-33725591
Centromeres are chromosomal loci where kinetochores assemble to ensure faithful chromosome segregation during mitosis. CENP-A defines the loci by serving as an epigenetic marker that recruits other centromere components for a functional structure. However, the mechanism that controls CENP-A regulation of centromeric chromatin integrity remains to be explored. Separate studies have shown that loss of CENP-A or the Cdk5 regulatory subunit associated protein 2 (Cdk5rap2), a key player in mitotic progression, triggers the occurrence of lagging chromosomes. This prompted us to investigate a potential link between CENP-A and Cdk5rap2 in the maintenance of centromeric chromatin integrity. Here, we demonstrate that loss of Cdk5rap2 causes reduced CENP-A expression while exogenous Cdk5rap2 expression in cells depleted of endogenous Cdk5rap2 restores CENP-A expression. Indeed, we show that Cdk5rap2 is a nuclear protein that acts as a positive transcriptional regulator of CENP-A. Cdk5rap2 interacts with the CENP-A promoter and upregulates CENP-A transcription. Accordingly, loss of Cdk5rap2 causes reduced level of centromeric CENP-A. Exogenous CENP-A expression partially inhibits the occurrence of lagging chromosomes in Cdk5rap2 knockdown cells, indicating that lagging chromosomes induced by loss of Cdk5rap2 is due, in part, to loss of CENP-A. Aside from manifesting lagging chromosomes, cells depleted of Cdk5rap2, and thus CENP-A, show increased micronuclei and chromatin bridge formation. Altogether, our findings indicate that Cdk5rap2 serves to maintain centromeric chromatin integrity partly through CENP-A.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cromatina / Activación Transcripcional / Centrómero / Proteínas de Ciclo Celular / Proteína A Centromérica / Proteínas del Tejido Nervioso Límite: Humans / Male Idioma: En Revista: Biomed Pharmacother Año: 2021 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Francia
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cromatina / Activación Transcripcional / Centrómero / Proteínas de Ciclo Celular / Proteína A Centromérica / Proteínas del Tejido Nervioso Límite: Humans / Male Idioma: En Revista: Biomed Pharmacother Año: 2021 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Francia