36
Views
23
CrossRef citations to date
0
Altmetric
Article

TRF1 Ensures the Centromeric Function of Aurora-B and Proper Chromosome Segregation

, , &
Pages 2464-2478 | Received 04 Feb 2014, Accepted 13 Apr 2014, Published online: 20 Mar 2023
 

Abstract

A cancer is a robustly evolving cell population originating from a normal diploid cell. Improper chromosome segregation causes aneuploidy, a driving force of cancer development and malignant progression. Telomeric repeat binding factor 1 (TRF1) has been established as a telomeric protein that negatively regulates telomere elongation by telomerase and promotes efficient DNA replication at telomeres. Intriguingly, overexpression of a mitotic kinase, Aurora-A, compromises efficient microtubule-kinetochore attachment in a TRF1-dependent manner. However, the precise role of TRF1 in mitosis remains elusive. Here we demonstrate that TRF1 is required for the centromeric function of Aurora-B, which ensures proper chromosome segregation. TRF1 depletion abolishes centromeric recruitment of Aurora-B and loosens sister centromere cohesion, resulting in the induction of merotelic kinetochore attachments, lagging chromosomes, and micronuclei. Accordingly, an absence of TRF1 in human and mouse diploid cells induces aneuploidy. These phenomena seem to be telomere independent, because a telomere-unbound TRF1 mutant can suppress the TRF1 knockdown phenotype. These observations indicate that TRF1 regulates the rigidity of the microtubule-kinetochore attachment, contributing to proper chromosome segregation and the maintenance of genomic integrity.

SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at http://dx.doi.org/10.1128/MCB.00161-14.

ACKNOWLEDGMENTS

We thank Kazuhiko Uchida and Kentaro Takagaki (JFCR Cancer Institute, Tokyo, Japan) for providing technical advice on time-lapse microscopy and analytical methods, Toru Hirota (JFCR Cancer Institute, Tokyo, Japan) for the HeLa-Kyoto cells expressing histone H2B-EGFP, HeLa-Kyoto cells coexpressing EGFP–CENP-A and EGFP–α-tubulin, and anti-CREST serum, and Yoichi Shinkai (RIKEN Advanced Science Institute, Saitama, Japan) for the conditionally mTRF1-deficient ES cells and anti-mTRF1 antibody.

This work was funded in part by MEXT KAKENHI grant 23117527 and by JSPS KAKENHI grant 22300341 (to H. Seimiya).

Log in via your institution

Log in to Taylor & Francis Online

PDF download + Online access

  • 48 hours access to article PDF & online version
  • Article PDF can be downloaded
  • Article PDF can be printed
USD 61.00 Add to cart

Issue Purchase

  • 30 days online access to complete issue
  • Article PDFs can be downloaded
  • Article PDFs can be printed
USD 265.00 Add to cart

* Local tax will be added as applicable

Related Research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.