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#metaphase

19 public questions tagged with this topic.

Cell Division

Which phase of mitosis is characterized by alignment of chromosomes at the metaphase plate?

Metaphase defined by alignment of condensed chromosomes along equatorial plate equidistant between spindle poles is visually hallmark of mitosis used for karyotyping. Following prometaphase, chromosomes undergo congression driven by opposing forces: CENP-E plus-end-directed kinesin transporting chromosomes toward plate, and dynein mediated poleward force, plus dynamic instability of microtubules causing oscillations. Correct amphitelic attachment where sister kinetochores bind microtubule bundles emanating from opposite centrosomes generates tension across centromere stretching inter-kinetochore distance, satisfying checkpoint. Erroneous syntelic or merotelic attachments lacking tension are destabilized by Aurora B kinase concentrated at inner centromere phosphorylating Ndc80 and KNL1 reducing microtubule affinity, giving second chance for proper biorientation. When all chromosomes aligned, metaphase plate forms, cyclin B-CDK1 activity remains maximal maintaining condensin activity and securin stability, and spindle assembly checkpoint silences awaiting anaphase trigger, ensuring synchronous segregation for equal genome distribution. This circuitry is highly conserved across eukaryotes, integrating growth factor signals, DNA damage surveillance, and developmental cues, and its disruption frequently underlies oncogenesis, providing targets for checkpoint inhibitors and cancer therapeutics.

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 17, Metaphase Alignment Mechanisms.

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Cell Cycle Regulation

Which regulatory factor is crucial for the metaphase-to-anaphase transition?

Metaphase to anaphase transition represents irreversible commitment executed by APC/C bound to Cdc20 coactivator. Throughout prometaphase chromosomes attach via kinetochores, generating unattached kinetochore signal converting Mad2 to active inhibitor forming mitotic checkpoint complex with BubR1, Bub3, and Cdc20 that binds APC/C core to block E2 recruitment. Upon achievement of biorientation of all chromosomes and establishment of tension, checkpoint protein recruitment stops, complex disassembles, and free Cdc20 associates with phosphorylated APC/C previously primed by CDK1 and Plk1. Active APC/C-Cdc20 polyubiquitinates securin and cyclin B with K11 chains for proteasomal destruction. Securin normally binds and locks separase protease in inactive conformation together with cyclin B-CDK1 phosphorylation. Degradation liberates separase that cleaves kleisin Rad21 subunit of cohesin ring embracing sister chromatids since S phase, opening ring, while cyclin B destruction drops CDK1 activity permitting phosphatase activation and mitotic exit. Blocking securin degradation prevents chromatid separation. This circuitry is highly conserved across eukaryotes, integrating growth factor signals, DNA damage surveillance, and developmental cues, and its disruption frequently underlies oncogenesis, providing targets for checkpoint inhibitors and cancer therapeutics.

Ref: Peters et al., Cell 1998, APC/C Regulation. Musacchio, Nat Rev Mol Cell Biol 2011, Anaphase.

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Cell Cycle Regulation

The metaphase-to-anaphase transition is triggered by:

The metaphase to anaphase transition is irreversible decision point governed by ubiquitin dependent proteolysis. When every chromosome achieves amphitelic kinetochore-microtubule attachment generating inter-kinetochore tension, spindle assembly checkpoint signaling through MCC production ceases. Dynein-mediated stripping of Mad1-Mad2 from kinetochores and p31comet-TRIP13 catalyzed MCC disassembly liberate coactivator Cdc20, enabling APC/C-Cdc20 ligase activation. Active APC/C polyubiquitinates securin via destruction box motif and cyclin B via D-box for rapid degradation by 26S proteasome. Securin degradation frees separase cysteine protease previously held as pseudosubstrate, while cyclin B destruction reduces CDK1 activity permitting dephosphorylation of mitotic substrates by PP1 and PP2A-B55. Free separase cleaves kleisin subunit Scc1 or Rad21 of cohesin tetramer encircling sister chromatids at centromeres rescued from earlier Wapl-mediated arm removal by Shugoshin-PP2A protection. Opening of cohesin ring dissolves linkage, allowing poleward microtubule pulling forces to separate sisters. Chromatid movement manifests as anaphase A toward poles and anaphase B spindle elongation driven by Eg5 kinesin and cortical dynein. Additional feedback loops involving polo-like kinases, phosphatases and SCF-mediated degradation reinforce irreversibility and protect against premature progression that would compromise genome integrity and viability.

Ref: Peters, Anaphase Promoting Complex Orchestrating Metaphase-Anaphase Transition, Nat Rev Mol Cell Biol 2006; Alberts et al., Chapter 18, Anaphase.

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