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Centromere Structure and Function

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Book cover Centromeres and Kinetochores

Part of the book series: Progress in Molecular and Subcellular Biology ((PMSB,volume 56))

Abstract

The centromere is the genetic locus that specifies the site of kinetochore assembly, where the chromosome will attach to the kinetochore microtubule. The pericentromere is the physical region responsible for the geometry of bi-oriented sister kinetochores in metaphase. In budding yeast the 125 bp point centromere is sufficient to specify kinetochore assembly. The flanking region is enriched (3X) in cohesin and condensin relative to the remaining chromosome arms. The enrichment spans about 30–50 kb around each centromere. We refer to the flanking chromatin as the pericentromere in yeast. In mammals, a 5–10 Mb region dictates where the kinetochore is built. The kinetochore interacts with a very small fraction of DNA on the surface of the centromeric region. The remainder of the centromere lies between the sister kinetochores. This is typically called centromere chromatin. The chromatin sites that directly interface to microtubules cannot be identified due to the repeated sequence within the mammalian centromere. However in both yeast and mammals, the total amount of DNA between the sites of microtubule attachment in metaphase is highly conserved. In yeast the 16 chromosomes are clustered into a 250 nm diameter region, and 800 kb (16 × 50 kb) or ~1 Mb of DNA lies between sister kinetochores. In mammals, 5–10 Mb lies between sister kinetochores. In both organisms the sister kinetochores are separated by about 1 μm. Thus, centromeres of different organisms differ in how they specify kinetochore assembly, but there may be important centromere chromatin functions that are conserved throughout phylogeny. Recently, centromeric chromatin has been reconstituted in vitro using alpha satellite DNA revealing unexpected features of centromeric DNA organization, replication, and response to stress. We will focus on the conserved features of centromere in this review.

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Authors and Affiliations

  1. Department of Biology, University of North Carolina at Chapel Hill, 623 Fordham Hall CB#3280, Chapel Hill, NC, 27599-3280, USA

    Kerry Bloom

  2. DNA Metabolism Laboratory, IFOM, The FIRC Institute of Molecular Oncology, Vai Adamello 16, 21139, Milan, Italy

    Vincenzo Costanzo

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  1. Kerry Bloom
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  2. Vincenzo Costanzo
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Correspondence to Kerry Bloom .

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  1. Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Ben E. Black

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Bloom, K., Costanzo, V. (2017). Centromere Structure and Function. In: Black, B. (eds) Centromeres and Kinetochores. Progress in Molecular and Subcellular Biology, vol 56. Springer, Cham. https://doi.org/10.1007/978-3-319-58592-5_21

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