RESEARCH ARTICLE Modeling the septation initiation network (SIN) in fission yeast cells Attila Csika ´sz-Nagy Æ Orsolya Kapuy Æ Be ´la Gy} orffy Æ John J. Tyson Æ Be ´la Nova ´k Received: 21 December 2006 / Revised: 16 January 2007 / Accepted: 30 January 2007 / Published online: 6 March 2007 Ó Springer-Verlag 2007 Abstract Cytokinesis in fission yeast is controlled by a signal transduction pathway called the Septation Initiation Network (SIN). From a dynamical point of view the most interesting questions about the regulation of fission yeast cytokinesis are: how do wild type cells ensure that septa- tion is initiated only once per cycle? Why does the control system stay in a continuously septating state in some mu- tant strains? And how is it that the SIN remains active when cytokinesis fails? To answer these questions we construct a simplified mathematical model of the SIN and graft this regulatory module onto our previous model of cyclin-dependent kinase (Cdk) dynamics in fission yeast cells. The SIN is both activated and inhibited by mitotic Cdk/cyclin complexes. As a consequence of this dual regulation, the SIN gets activated only once at the end of mitosis, when Cdk activity drops. The mathematical model describes the timing of septation not only in wild type cells but also in mutants where components of the SIN are knocked out. The model predicts phenotypes of some un- characterized mutant cells and shows how a cytokinesis checkpoint can stop the cell cycle if septation fails. Keywords Adaptation  Simulation  Cytokinesis  Schizosaccharomyces pombe  Cell cycle Abbreviations SIN Septation initiation network SPF S-phase promoting factor MPF M-phase promoting factor CDK Cyclin dependent kinase SPB Spindle pole body GEF Guanine nucleotide exchange factor GAP GTPase activating protein Introduction During the growth-and-division cycle, a cell must replicate all of its components and divide them into two nearly identical daughter cells. Successful completion of this complex task requires the coordination of many processes. Some of these events (mostly related to cytoplasmic growth) happen continuously, while others take place only at specific times during the cell cycle. Temporally specific events —DNA replication (S phase), mitosis (M phase) and cell division (cytokinesis)—must take place only once per cycle and in the correct order. In this paper we use math- ematical models to study the molecular regulatory network responsible for triggering cell division once and only once per cell cycle. Communicated by S. Hohmann. Electronic supplementary material The online version of this article (doi:10.1007/s00294-007-0123-4) contains supplementary material, which is available to authorized users. A. Csika ´sz-Nagy (&)  O. Kapuy  B. Gy} orffy  B. Nova ´k Materials Structure and Modeling Research Group of the Hungarian Academy of Sciences and Department of Applied Biotechnology and Food Science, Budapest University of Technology and Economics, 1111 Budapest, Szt. Gelle ´rt te ´r 4, Hungary e-mail: csikasz@mail.bme.hu URL: http://www.cellcycle.bme.hu/ J. J. Tyson Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA 123 Curr Genet (2007) 51:245–255 DOI 10.1007/s00294-007-0123-4