Signaling Pathways that Regulate Cell Division

Cell division requires careful orchestration of three major events: entry into mitosis, chromosomal segregation, and cytokinesis. Signaling within and between the molecules that control these events allows for their coordination via checkpoints, a specific class of signaling pathways that ensure the dependency of cell-cycle events on the successful completion of preceding events. Multiple positive-and negative-feedback loops ensure that a cell is fully committed to division and that the events occur in the proper order. Unlike other signaling pathways, which integrate external inputs to decide whether to execute a given process, signaling at cell division is largely dedicated to completing a decision made in G1 phase-to initiate and complete a round of mitotic cell division. Instead of deciding if the events of cell division will take place, these signaling pathways entrain these events to the activation of the cell-cycle kinase cyclin-dependent kinase 1 (CDK1) and provide the opportunity for checkpoint proteins to arrest cell division if things go wrong. Outline 1 Introduction 2 CDK1 and entry into mitosis 3 Regulation of the G2/M transition 4 Checkpoint regulation of the G2/M transition 5 The DNA damage and replication checkpoints 6 The DNA damage checkpoint triggered by DSBs 7 The DNA replication checkpoint triggered by stalled replication forks 8 Chk1 and Chk2 target Cdc25 9 The MAPK-dependent stress checkpoint 10 Resolution of G2 checkpoint arrests 11 Regulation of mitosis 12 Dissecting the network 13 Anaphase entry 14 Checkpoint regulation of mitosis 15 Regulation of cytokinesis