Centriole Duplication at the Crossroads of Cell Cycle Control and Oncogenesis

Abstract

Centriole duplication is a vital process for cellular organisation and function, underpinning essential activities such as cell division, microtubule organisation and ciliogenesis. This review summarises the latest research on the mechanisms and regulatory pathways that control this process, focusing on important proteins such as polo-like kinase 4 (PLK4), SCL/TAL1 interrupting locus (STIL) and spindle assembly abnormal protein 6 (SAS-6). This study examines the complex steps involved in semi-conservative duplication, from initiation in the G1-S phase to the maturation of centrioles during the cell cycle. Additionally, we will explore the consequences of dysregulated centriole duplication. Dysregulation of this process can lead to centrosome amplification and subsequent chromosomal instability. These factors are implicated in several cancers and developmental disorders. By integrating recent study findings, this review emphasises the importance of centriole duplication in maintaining cellular homeostasis and its potential as a therapeutic target in disease contexts. The presented findings aim to provide a fundamental understanding that may inform future research directions and clinical interventions related to centriole biology.

Keywords: cell cycle control; centriole duplication; chromosomal instability; ciliopathies; oncogenesis.

Figure 6

The initiation of centriole duplication, which involves the assembly of the cartwheel through the sequential binding of PLK4, STIL and SAS6.

Figure 1

A barrel-shaped centriole displaying nine-fold symmetry and consisting of nine microtubule triplets. ‘A’ represents a complete microtubule, while ‘B’ and ‘C’ represent incomplete microtubules. The triplets are located at the base of the centriole, while the distal end consists of doublets.

Figure 2

A G1 centrosome consists of a mother centriole with its distal and subdistal appendages, as well as a daughter centriole that lacks appendages. Both are associated with a linker and are surrounded by pericentriolar material (PCM).

Figure 3

Centriole duplication, which starts with new procentrioles growing at the surface of each old centriole that remains associated by a linker.

Figure 4

Cell division in Ascaris megalocephala, drawn by Theodor Boveri in 1901 from his observations using high optical enlargement.

Figure 5

The synchronisation of the DNA cycle (light grey) and the centriole cycle (dark grey). Note that the cell cycle is divided into G1, S, G2 and M phases, which are defined in relation to the DNA cycle.

Figure 7

In interphase, mother and daughter centrioles remain associated by a fibrous structure called the linker, which is made up of Rootletin (shown in blue) that is bound to C-Nap1 (shown in red) at the proximal ends of the centrioles. The removal of the linker is achieved through a complex mechanism that mainly depends on C-Nap1 phosphorylation by Nek2A.

Figure 8

The six stages of centriole duplication during the cell cycle. (DC: daughter centriole; MC: mother centriole). The stages are disengagement, initiation and immediate re-engagement, elongation, splitting, maturation and segregation.

Figure 9

The nine-fold symmetry structure of the cartwheel, detailing the self-assembly of SAS-6 dimers.

Figure 10

The cartwheel assembly with its nine triplets of microtubules. SAS-6 dimers are shown in black, CPAP in green and CEP35 in red.