Ensuring the faithful execution of cytokinesis in Schizosaccharomyces pombe

Abstract

Eukaryotic cells ensure error-free progress through the cell cycle by monitoring (1) the completion of cell cycle events, (2) damage to critical cellular components, or (3) structural changes such as the attachment of kinetochores to the mitotic spindle. In the presence of damage, or in the face of a reduced capacity to complete essential events, cells are capable of delaying the cell cycle so that damage can be repaired, or previous cell cycle phases can proceed to completion. Although such "checkpoints" have been extensively studied in many organisms-and much is understood with respect to the monitoring of DNA replication and DNA damage-little is known with regards to mechanisms that might monitor the completion of cytokinesis. In this review I summarize recent work from the fission yeast, Schizosaccharomyces pombe, describing the existence of regulatory modules that aid in ensuring the faithful and reliable execution of cytokinesis. Together, these modules promote the maintenance of a "cytokinesis-competent" state characterized by delayed progression into mitosis and the continuous repair and/or re-establishment of the acto-myosin ring. In this way, fission yeast cells are able to increase the likelihood of successful cell division prior to committing to a subsequent cell cycle. The recent demonstration of conservation between S. pombe components of these modules, and human proteins with defined roles in preventing cell division failure, suggest that the lessons learned in S. pombe may be applicable to other eukaryotes.

Keywords: cell division; cytokinesis; cytokinetic actomyosin ring; fission yeast; genomic integrity.

Figure 1. Regulatory dynamics during cytokinesis in S. pombe. (A) During interphase, Mbx1p, a component of the pombe cell cycle box binding factor (PBF), is bound and dephosphorylated by Clp1p. In this form Mbx1p aids in repression of the transcription of a set of genes (including mid1, sid2, and cdc15) with roles in cytokinesis. (B) During normal cytokinesis—or upon extension of the cytokinetic (or “C”) phase of the cell cycle upon perturbation of the cell division machinery—Plo1p phosphorylates Mbx1p, relieving its inhibitory effect on the transcription of cytokinesis genes such as sid2. Sid2p phosphorylates Clp1p, creating a binding site for the 14-3-3 protein, Rad24p. Rad24p binding to Clp1p promotes the cytoplasmic retention of Clp1p, preventing it from de-phosphorylating Mbx1p.