Chromosome Cohesion and Condensation

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Chromosome Cohesion and Condensation

• Interphase functions that are essential for
  successful chromosome segregation

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Slice from a cryo-tomogram of a 120nm frozen
section cut from a mammalian cell, NRK
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An overview of the chromosome cycle
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Primary solution to the length problem
Opening Image from Chapter 4
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Secondary solution compaction of nucleosomes
into the 10 nm fiber
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Higher order solutions are still obscure, but
additional problems with chromosome organization
are obvious

• Some chromatin domains are active and others are
  not. Experiments indicate that inactive
  chromatin is condensed. How?
• The efficiency of DNA repair in G2, even DSBs,
  implies that homologous or even identical DNA is
  near by. How?
• At mitosis, sister chromatids must segregate from
  one another. How?

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The problem of maintaining an association
between sister chromatids, so as to make
a functional mitotic chromosome
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Chromosome Structure in cell division
Sister Chromatid Cohesion
Condensation
Sumner, 1991
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Yeast chromosome structurean oxymoron?
Vertebrate Mitotic chromosomes
Budding yeast Mitotic chromosomes
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A route to answers for these questions has come
with discovery of two protein complexes,
condensin and cohesin

• Genetic screens in yeasts and biochemistry in
  extracts from Xenopus eggs have identified the
  protein subunits of these two complexes
• Both contain isoforms of the proteins SMC or
  Structural Maintenance of Chromosomes

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SMCs have now been discovered in virtually all
organisms, suggesting great importance

• Budding yeasts were first
• Fission yeasts soon thereafter
• Xenopus egg extracts
• Bacteria both E. coli and B. subtilis
• Then humans, plants, and everyone else

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Structural Maintenance Chromosomes
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Models for cohesin complex installation and
function
Embrace
Open Close the ring
Snap
DNA binding
Dimerization/ oligomerization
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Removal of cohesin in mitosis
Cohesin
Cohesin degradation by separase
Cdc5 (Polo)
Cen
Ipl1 (Aurora)
Sister chromatids
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A view of Condensin structure and
diversityTatsuya HiranoCurrent Biol.
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Localization of the condensin complex a) normal
metaphase b) metaphase arrest with a spindle
poison
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Hypothetical views of Chr. condensation
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Condensin in action?
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Results from failures in condensation
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SMC Complex
Function
Cohesin
Sister chromatid cohesion
Condensation
Condensin
Gene Expression
Dosage Compensation
MRX
DNA Repair Replication
MukB
Bacterial Segregation
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Assembly of DSB specific cohesin domain
cohesin
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Taking out the gene names
cohesin
When
Where
Cohesin loading factor
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Function for DSB specific cohesin domain?
cohesin
Mre11
Efficient post replicative repair?
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Understanding meiotic chromosome structure
through cohesin and condensin
DNA
cohesin
condensin
DNA
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Condensin facilitates assembly of the axial
element
Hop1
Ycs4-HA
wild type condensin
Red1
Ycs4-HA
Hop1
Rec8-HA
ycs4-s
Red1
Rec8-HA
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Condensin and Cohesin as platform forS.C.
assembly
Mitosis
Meiosis
Chromosome organization
Chromosome organization
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Regulated cohesin removal in Meiosis 1
Cen
Cohesin
Sister chromatids
Homologs
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SMCs may play a role in regulation of local
chromatin compaction