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#kinetochore

3 public questions tagged with this topic.

Nucleosome Packing

CENP-A mainly localizes to:

CENP-A containing nucleosomes localize almost exclusively to functional centromere, not dispersed throughout chromosome arms. High resolution immunofluorescence and chromatin immunoprecipitation sequencing show discrete foci at primary constriction colocalizing with inner kinetochore markers CENP-C and CENP-T during interphase and mitosis. At centromere CENP-A directly recruits CCAN network initiating kinetochore assembly ensuring spindle microtubule attachment and checkpoint signaling. It does not accumulate at telomeres containing TTAGGG repeats protected by shelterin, nor at nucleolar organizer regions containing rDNA, nor at replication origins firing genome wide.

Ref: Earnshaw and Migeon CENP-A Localization; Lodish et al., Chapter 19: CENP-A Mainly Localizes to Centromere

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Eukaryotic chromatin and chromosome

Kinetochore assembles at:

Kinetochore is large multiprotein structure assembling exclusively at centromeric chromatin containing CENP-A nucleosomes. During mitosis inner kinetochore components CENP-C, CENP-T, CENP-I constitutively associate with centromere, outer KMN network including Ndc80, Mis12, KNL1 complexes binds plus ends of spindle microtubules. This linkage transmits pulling forces to separate sister chromatids and activates spindle assembly checkpoint via Mad2, BubR1 until biorientation achieved. Telomeres cap ends, replication origins fire throughout genome, NORs build nucleolus, whereas kinetochore location solely defines segregation platform at centromere region.

Ref: Cheeseman and Desai 2008 Nat Rev Mol Cell Biol; Lodish et al., Chapter 19: Kinetochore Assembles at Centromere

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Eukaryotic chromatin and chromosome

Centromere function is:

Centromeres provide mechanical linkage essential for chromosome segregation. At centromeric DNA, histone H3 variant CENP-A replaces canonical H3 assembling specialized nucleosomes that directly recruit constitutive centromere associated network CCAN proteins including CENP-C and CENP-T. This platform builds kinetochore, large multiprotein structure containing KMN network that captures spindle microtubule plus ends during mitosis and meiosis. It ensures biorientation, tension sensing via Aurora B kinase and equal segregation. Without functional centromere kinetochore cannot assemble leading to aneuploidy, unlike roles in replication or telomere maintenance pathways.

Ref: Lodish et al., Molecular Cell Biology, 9th ed., Chapter 19: Centromere Function - Spindle Attachment via Kinetochore

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