Skip to content
Login Register

#chromosome attachment

3 public questions tagged with this topic.

Cell Division

How do mitotic spindles attach to chromosomes?

Faithful chromosome segregation depends on physical linkage between centromeric DNA and spindle microtubules via kinetochore large protein machine exceeding 100 components organized into layered architecture. Inner kinetochore permanently bound to centromere during cell cycle contains constitutive centromere-associated network including CENP-C that recognizes CENP-A nucleosome, plus CENP-T-W-S-X tetramer forming DNA binding module with histone-like fold. Outer kinetochore assembled specifically in mitosis contains KMN network: Knl1 scaffold with MELT motifs recruiting checkpoint proteins, Mis1

Ref: Cheeseman & Desai, Annu Rev Cell Dev Biol 2008, Kinetochore Structure. Musacchio & Desai, Biology 2017.

View Details
Cell Cycle Regulation

What is the correct type of attachment between chromosomes and microtubules?

Kinetochore-microtubule interactions evolve through search and capture mechanism mediated by dynamic microtubule instability. Successful biorientation defined as amphitelic configuration where sister kinetochores attached to microtubules originating from opposite spindle poles. This arrangement produces pulling forces toward poles resisted by centromeric cohesin complex linking sisters, generating inter-kinetochore tension about 0.5 to 1 micron stretch detectable as separation between CENP-A foci. Tension acts as stabilization signal and silences spindle checkpoint. By contrast monotelic state

Ref: Cimini, Merotelic Attachment and Chromosome Missegregation, Curr Biol 2008; Alberts et al., Molecular Biology of the Cell, Chapter 17, Chromosome Alignment.

View Details
Cell Cycle Regulation

Which protein complex silences the spindle checkpoint once all chromosomes are attached?

Silencing of spindle assembly checkpoint once all chromosomes achieve correct bi-orientation requires active disassembly of mitotic checkpoint complex and removal of checkpoint proteins from attached kinetochores. Central regulator is p31comet, also called MAD2L1BP, adaptor that binds closed conformation of Mad2 within MCC and recruits ATPase TRIP13 (Pch2 in yeast). TRIP13 uses ATP hydrolysis to convert closed Mad2 back to open inactive form, promoting disassociation of BubR1-Bub3-Cdc20 complex and freeing Cdc20 to activate APC/C. p31comet also competes with Mad1 for Mad2 binding, preventing n

Ref: Mapelli & Musacchio, EMBO J 2007, p31comet and TRIP13; Eytan et al., PNAS 2014, MCC Disassembly.

View Details