The nucleus serves as the pacemaker for the cell cycle

Oshri Afanzar,Garrison K Buss,James E Ferrell,Tim Stearns

doi:10.7554/elife.59989

Abstract

Mitosis is a dramatic process that affects all parts of the cell. It is driven by an oscillator whose various components are localized in the nucleus, centrosome, and cytoplasm. In principle, the cellular location with the fastest intrinsic rhythm should act as a pacemaker for the process. Here we traced the waves of tubulin polymerization and depolymerization that occur at mitotic entry and exit in Xenopus egg extracts back to their origins. We found that mitosis was commonly initiated at sperm-derived nuclei and their accompanying centrosomes. The cell cycle was ~20% faster at these initiation points than in the slowest regions of the extract. Nuclei produced from phage DNA, which did not possess centrosomes, also acted as trigger wave sources, but purified centrosomes in the absence of nuclei did not. We conclude that the nucleus accelerates mitotic entry and propose that it acts as a pacemaker for cell cycle.

Highlights

Mitotic entry is driven by a circuit of proteins that regulates cyclin-dependent protein kinase-1 (Cdk1) and its opposing phosphatases
We identified the last 15% of the pixels to enter mitosis, which often were regions that appeared not to have been entrained by a trigger wave (Figure 2B, green)
We used Xenopus egg extracts and reconstitution to determine what structure acts as pacemaker for the mitotic oscillator

Summary

Introduction

Mitotic entry is driven by a circuit of proteins that regulates cyclin-dependent protein kinase-1 (Cdk1) and its opposing phosphatases. Heartbeats originate at the sinoatrial node, which has a typical frequency of 60–90 minÀ1 in humans, and spread to and override the slower rhythms of the atrioventricular node (whose intrinsic frequency is 40–60 minÀ1) and ventricles (30–40 minÀ1) (Pappano and Wier, 2019) At present, it is uncertain where mitotic trigger waves begin. Studies with FRET probes microinjected into mammalian cells have suggested that mitosis might be initiated in all parts of the cell essentially simultaneously (Gavet and Pines, 2010) This may well be true for somatic cells, where distances are on the order of 10 mm, whereas in larger cells like frog eggs it is clear that mitotic events happen in different parts of the cell at different times (Chang and Ferrell, 2013; Hara et al, 1980). These experiments demonstrate that the nucleus acts as the pacemaker for the Xenopus embryonic cell cycle

Results

Discussion

Materials and methods