Practice question

Spontaneous microtubule assembly from alpha-beta tubulin heterodimers is kinetically unfavorable due to nucleation barrier requiring oligomeric seed. Centrosomes overcome this via gamma-tubulin ring complex, dominant template in animal cells. Gamma-TuRC assembles as 14 nm wide lock-washer containing about 14 gamma-tubulin molecules positioned with GCP2-6 proteins, namely GCP2, GCP3 forming gamma-TuSC repeats plus GCP4, GCP5, GCP6, plus actin and MZT1/2 small proteins. Structure mirrors 13-protofilament microtubule lattice with minus end capped. Localized within pericentriolar material through adaptors pericentrin, CDK5RAP2, CEP192, gamma-TuRC provides lateral contacts stabilizing nascent tubulin dimers, lowering critical concentration for polymerization and defining polarity with plus ends outward. Nucleation capacity expands dramatically at G2/M when CDK1, Plk1 and Aurora A mediated phosphorylation increases PCM recruitment. During mitosis, several hundred complexes per centrosome generate astral and spindle microtubules. Branching nucleation via augmin complex using existing microtubules further amplifies spindle density. Defective gamma-TuRC function leads to weak asters, monopolar spindles and failure of chromosome congression. 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.