Triple deletion of TP53, PCNT, and CEP215 promotes centriole amplification in the M phase

Cell Cycle. 2021 Aug;20(15):1500-1517. doi: 10.1080/15384101.2021.1950386. Epub 2021 Jul 8.

Abstract

Supernumerary centrioles are frequently observed in diverse types of cancer cells. In this study, we investigated the mechanism underlying the generation of supernumerary centrioles during the M phase. We generated the TP53;PCNT;CEP215 triple knockout (KO) cells and determined the configurations of the centriole during the cell cycle. The triple KO cells exhibited a precocious separation of centrioles and unscheduled centriole assembly in the M phase. Supernumerary centrioles in the triple KO cells were present throughout the cell cycle; however, among all the centrioles, only two maintained an intact composition, including CEP135, CEP192, CEP295 and CEP152. Intact centrioles were formed during the S phase and the rest of the centrioles may be generated during the M phase. M-phase-assembled centrioles lacked the ability to organize microtubules in the interphase; however, a fraction of them may acquire pericentriolar material to organize microtubules during the M phase. Taken together, our work reveals the heterogeneity of the supernumerary centrioles in the triple KO cells. .

Keywords: CEP215; Centrosome; PCNT; cell cycle; mitosis; supernumerary centrioles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens / genetics
  • Antigens / metabolism*
  • Cell Cycle Proteins / deficiency*
  • Cell Cycle Proteins / genetics
  • Cell Division*
  • Centrioles / genetics
  • Centrioles / metabolism*
  • Gene Deletion
  • Gene Knockout Techniques
  • HeLa Cells
  • Humans
  • Mitosis*
  • Nerve Tissue Proteins / deficiency*
  • Nerve Tissue Proteins / genetics
  • Signal Transduction
  • Tumor Suppressor Protein p53 / deficiency*
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Antigens
  • CDK5RAP2 protein, human
  • Cell Cycle Proteins
  • Nerve Tissue Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • pericentrin

Grants and funding

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government [No. NRF-2019R1A2C2002726].