PrometaphaseEdit
Prometaphase is a transitional stage in cell division that bridges prophase and metaphase. In cells undergoing open mitosis, the nuclear envelope breaks down, allowing spindle microtubules to interact with condensed chromosomes. Kinetochores on sister chromatids capture microtubules and drive the dynamic movements that bring chromosomes toward the center of the cell, where they will align along the metaphase plate. The duration and specifics of prometaphase vary among organisms and cell types, but the core feature is the onset of stable chromosome–microtubule attachments and the initiation of congression toward a single plane.
In many cells, prometaphase sets the stage for accurate chromosome segregation by coordinating motor forces, microtubule dynamics, and checkpoint surveillance. This phase is characterized by rapid reorganization of spindle architecture and by the establishment of bi-oriented attachments that generate tension across sister kinetochores. Incorrect attachments are destabilized and corrected before the cell progresses to anaphase, helping to prevent aneuploidy. Key components include spindle poles, microtubules, kinetochores, and a suite of motor proteins and regulatory kinases that monitor attachment status and chromosome tension. mitosis spindle apparatus kinetochore microtubule spindle assembly checkpoint
Overview
Prometaphase is defined by the disassembly of the nuclear envelope in organisms that undergo open mitosis, enabling microtubules to encounter and engage chromosomes. Early in prometaphase, kinetochores establish initial, often lateral, attachments to microtubules and then mature into end-on connections that can sustain chromosome movement toward the spindle equator. The chromosomes begin their journey from peripheral positions toward the center, a process driven by a combination of microtubule growth and shrinkage, poleward forces, and chromosomal motors. The orchestration of these forces ensures chromosomes are positioned for the next stage, metaphase, where they align at the metaphase plate and are held in place before separation. nuclear envelope chromosome centrosome spindle apparatus
Kinetochore–microtubule interactions
A central event of prometaphase is the capture of kinetochores by spindle microtubules. Microtubules search the cellular space, and once a kinetochore–microtubule connection forms, the chromosome can begin to move toward the spindle. Attachments progress from lateral to end-on, and proper bi-oriented attachments—where sister kinetochores attach to microtubules from opposite poles—generate tension that stabilizes these connections. If attachments are incorrect, such as syntelic or merotelic configurations, the interactions are destabilized and corrected via regulatory pathways, notably involving kinase activities that monitor attachment geometry and tension. This dynamic quality of prometaphase is a test bed for the fidelity of chromosome segregation. kinetochore microtubule bi-oriented attachment merotelic attachment syntelic attachment Aurora B kinase
Mechanisms of movement rely on a cadre of motor proteins and dynamic instability of microtubules. Dynein motors contribute to initial poleward movements and help focus spindle poles, while plus-end–directed kinesins, including those moving toward the microtubule plus ends, drive chromosome congression and alignment. In many systems, kinesin-5 family members create outward forces that promote spindle separation, and kinesin-7 and related motors assist with stable end-on attachments and error correction. Chromokinesins on chromosome arms can produce polar ejection forces that help position chromosomes within the nucleus before they attach firmly to microtubules. These activities are coordinated with the regulation of microtubule dynamics, including rates of growth and catastrophe at microtubule ends. dynein kinesin-5 kinesin-7 chromokinesin
Checkpoints and error correction
A crucial feature of prometaphase is the surveillance of attachment quality by the spindle assembly checkpoint (SAC). Kinetochores must achieve proper, tensioned bi-orientation to silence the checkpoint and permit progression to anaphase. The SAC responds to unattached kinetochores or to improper attachments by delaying the cell cycle until correct connections are established. Protein networks involving checkpoint kinases, such as Mad and Bub proteins, monitor attachment status and coordinate the timing of anaphase onset with the establishment of correct kinetochore–microtubule attachments. Aurora B kinase plays a key role in detecting and promoting the turnover of incorrect attachments, ensuring that error correction proceeds during prometaphase and metaphase. spindle assembly checkpoint Mad2 Bub1 Aurora B kinase Ndc80 complex
Open versus closed mitosis and organismal variation
Prometaphase behavior varies across organisms. In organisms that undergo open mitosis, the nuclear envelope breaks down, and chromosomes engage the spindle in a dynamic, radiating environment. In organisms with closed mitosis, such as many yeasts, the nucleus remains intact, and prometaphase-like events occur within a consolidated nuclear compartment. Plants, animals, and many fungi exemplify open mitosis, whereas some unicellular eukaryotes preserve a closed nuclear envelope during division. These differences influence how microtubules access chromosomes, how spindle poles are organized, and how checkpoints regulate attachment and timing. open mitosis yeast closed mitosis
Historical context and models
The concept of prometaphase as a distinct mitotic stage emerged from light- and electron-microscopy studies that charted progressive chromosome behavior during mitosis. Early descriptions highlighted the breakdown of the nuclear envelope and the formation of a spindle capable of capturing chromosomes. Over time, advances in live-cell imaging and molecular genetics clarified the contributions of motor proteins, microtubule dynamics, and checkpoint signaling to the prometaphase program. Contemporary models describe prometaphase as a dynamic balance between attachment formation, error correction, and motor-driven movements that in concert set up the cell for the orderly segregation of genetic material. mitosis cell cycle kinetochore spindle assembly checkpoint