Molecular Genetics

Identification of centromere sequences led to the realization that they are not conserved in evolution.

Facts

• In S. cerevisiae, deletion and mutagenesis of CEN's revealed that they consist of about 125 bp (less than 0.1% of the length of the chromosome. The CEN consists of three regions, CDEI, CDEII, and CDEIII. Region I is not essential for CEN function, but plays an enhancing role. Region II is AT rich and binds histone-like proteins. Region III is essential. Morphological observation suggests a single microtubule binds at each centromere. Kinetochores are indistinct in this yeast.

• In S. pombe, deletion and mutagenesis of CEN's revealed that they consist of several kbp of DNA (1 to 2% of the chromosome). Each of the three CEN's has a central core sequence flanked by inverted repeats. Flanking the repeats are members of repeated sequence element families. Some are tandemly repeated. Others are interspersed with other repeats. S. pombe chromosomes have clearly recognizable kinetochores.

• Primate alpha satellite DNA, implicated in chromosome segregation, is a tandemly repeated family of 171 bp sequences concentrated in the centromeric regions. The genetic regions of Arabidopsis thaliana chromosomes identified as containing the centromeres consist of a tandemly repeated family of 180 bp sequences (ref).

• Caenorhabditis elegans chromosomes are holocentric, microtubules attaching at various places along each chromosome. Thus, despite the completion of the C. elegans genome sequence, no centromere-characteristic DNA sequences have been identified (Tyler-Smith & Floridia).
• A Drosophila centromere region consists of highly repeated DNA with islands of unique sequence DNA.
  • The Bora Bora region consists of an AATAT satellite with four embedded transposable elements.
  • The Bora Bora island is required for maximal efficiency of segregation.
  • Adjacent to Bora Bora is an AAGAG satellite with other embedded transposable elements in a region called Maupiti (not shown). Maupiti is essential for proper segregation.
  • Neither the satellites nor the transposable elements are common to all Drosophila centromeres.

Interpretations

• CEN structures vary widely from species to species. They may also vary from chromosome to chromosome within a species.
• The interchromosome variation suggests that a higher order structure rather than a primary sequence may be the feature that defines a centromere.
• In contrast to telomeres, CEN structures probably won't function across species barriers.

Further information

• Region III of the S. cerevisiae centromere is the site for binding of the CBF3 protein.
• Rice centromere regions consist of dispersed members of six moderately repeated DNA families and one tandemly repeated DNA (ref). The repeat unit of the latter, CentO, is 155 bp long and is particularly associated with chromosome misdivisions (ref).
• The structure of nucleosomes on centromeric DNA plays a role in centromere function. Hyperacetylation of histones by transient treatment with an inhibitor of the enzyme that removes acetyl groups results in improperly functioning centromeres. The hyperacetylated state is heritable.
• Pericentromeric regions are usually heterochromatic. In Schizosaccharomyces pombe the pericentromeric repeat sequences are transcribed in an overlapping fashion when the region is not silenced. The transcripts are non-coding and induce transcrptional gene silencing (ref).
• The CEN structure determines characteristics of spindle attachment.

This is page 1364 of Molecular Genetics by Ulrich Melcher, © 1997-2001, 2003-4
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