14.3 Control of the cell cycle 1. Checkpoint of the cell cycle and its regulation by cell growth and extracellular signals as well as by internal signaling, involving a series of cdc genes-related proteins The progreesion of cells through the cell cycle is regulated by extracellular signals from the environment as well as by internal signaling that monitor and coordinate the various processes that take place during different cell cycle phases There are two major events in the cell cycle, at which the control mechanisms of the cell are focused one is the initiation of DNA replication occurring at the transition between G, and S: and the other is the initiation of the mitosis inducing the condensation of the chromatin occurring at the transition between G, and M. Both of these events or stages as well as probably additional events represent control points in the cell cycle (refer to them as transition point, such as at
14.3 Control of the cell cycle 1. Checkpoint of the cell cycle and its regulation by cell growth and extracellular signals as well as by internal signaling, involving a series of cdc genes-related proteins. The progreesion of cells through the cell cycle is regulated by extracellular signals from the environment as well as by internal signaling that monitor and coordinate the various processes that take place during different cell cycle phases. There are two major events in the cell cycle, at which the control mechanisms of the cell are focused: one is the initiation of DNA replication occurring at the transition between G1 and S; and the other is the initiation of the mitosis, inducing the condensation of the chromatin occurring at the transition between G2 and M. Both of these events or stages, as well as probably additional events represent control points in the cell cycle (refer to them as transition point, such as at
the transition from G, to s phase refer to restriction point, R point for animal cell or START for yeast starting DNA replication). Namely, when a cell becomes committed to beginning a crucial event-initiating replication or entering mitosis, these points in cell cycle sever as checkpoints (G checkpoint at the transition between G and S, Gi checkpoint at the transition between G, and M)at which the cell can stop continued progress and check whether certain conditions have not been met and if certain critical processes have properly completed, such as check for cell size, nutrient growth factors and dna damage at G checkpoint and check for cell size, complement of DNA replication at G2 check point, or chromosomal alignment during M phase. For the arresting role of checkpoints, at least three distinct classes of proteins are required: (1) sensors detecting Situation and abnormalities during the different phase process and emit an
the transition from G1 to S phase refer to restriction point, R point for animal cell or START for yeast starting DNA replication). Namely, when a cell becomes committed to beginning a crucial event-initiating replication or entering mitosis, these points in cell cycle sever as checkpoints (G1 checkpoint at the transition between G1 and S, G1 checkpoint at the transition between G2 and M) at which the cell can stop continued progress and check whether certain conditions have not been met and if certain critical processes have properly completed, such as check for cell size, nutrient, growth factors and DNA damage at G1checkpoint and check for cell size, complement of DNA replication at G2 check- point, or chromosomal alignment during M phase. For the arresting role of checkpoints, at least three distinct classes of proteins are required: (1) sensors detecting situation and abnormalities during the different phase process and emit an
appropriate signal, such as a protein kinase encoded by ATM gene responsible for DNA damage(2)transmitter (i. e, checkpoint kinase, Chks) transferring signal along the proper signaling pathways( such as p53/p2 pathway)(3) effectors(such as p21) that exert the action of inhibiting cell cycle machinery(such as MPF complex see next sections). Passage through these checkpoints would be induced by grown cell size, nutrient supplement, in particular extracellular signals i.e. growth factors and regulated by the presence of optimal concentration of one or more cytoplasmic stimulatory factors, whose related gene called cell division cycle( cdc )gene, and re-trigger the cell cycle machinery, in particular, first re-trigger MPF
appropriate signal, such as a protein kinase encoded by ATM gene responsible for DNA damage (2) transmitter (i.e., checkpoint kinase, Chks) transferring signal along the proper signaling pathways( such as p53/p21pathway) (3) effectors (such as p21) that exert the action of inhibiting cell cycle machinery (such as MPF complex see next sections). Passage through these checkpoints would be induced by grown cell size, nutrient supplement, in particular extracellular signals i.e. growth factors and regulated by the presence of optimal concentration of one or more cytoplasmic stimulatory factors, whose related gene called cell division cycle ( cdc ) gene, and re-trigger the cell cycle machinery, in particular, first re-trigger MPF
Fi 14.8 Cell cycle checkpoints Several checkpoints function to ensure that complete genomes are transmitted to daughter cells. One ma ior checkpoint arrests cells in G in response to dam aged or unreplicated DNA. The pres ence of damaged dnA also leads to cell cycle arrest at a checkpoint CI( Another checkpoint, in M phase arrests mitosis if the daughter chromo somes are not properly aligned on the dle Unreplicated damaged DNA STOP misalignment Darmage DNA
Checkpoint and the events checked for Resting y Spindle Assembly Checkpoint state Check for: Chromosome attachment to spindle G2 Checkpe Check for Cell size · DNA rep| lication G2 G1 Checkpoint G1 Check for Cell size Nutrients Growth factors (DNA synthesis) · DNA damage Resting state(GO)
Checkpoint and the events checked for