In biology, the chromosome scaffold is the backbone that supports the structure of the chromosomes. It is composed of a group of non-histone proteins that are essential in the structure and maintenance of eukaryotic chromosomes throughout the cell cycle. These scaffold proteins are responsible for the condensation of chromatin during mitosis.[1]

Origin

In the late 1970s, Ulrich K. Laemmli and colleagues discovered a backbone structure in eukaryotic chromosomes after they depleted the histone proteins. This backbone was localized along the chromosome axis, and was termed the ‘chromosome scaffold’.[2][1]

Proteins of the scaffold

Immunodetection of a chromosome showing DNA (blue) and two scaffold proteins: SMC2 (red) and topoisomerase IIα (green)[1]

In eukaryotic organisms, the DNA of each cell is organized into separated chromosomes, which are composed of chromatin, a mixture of DNA and many different groups of proteins. Among them, the structural proteins (that are not histones) bind the chromatin fiber around themselves forming a long, continuous axis or backbone that gives the chromosomes their shape. For this reason they are known as the ‘scaffold’ of chromosomes.[1]

Three protein groups have been identified as the main components of the scaffold: DNA topoisomerase IIα, condensins, and the KIF4A kinesin. When these proteins are removed, the chromosome shape does not appear and the chromatin fibers spread out.[1]

Topoisomerase IIα

The enzyme DNA topoisomerase IIα prominently appears along the chromosome axis as part of the scaffold.[3] In mitosis, it is concentrated at the centromeres and the axis along the chromosome arms. It is thought that the protein has a role in untangling the DNA as the loops become more concentrated along the axis during the condensation of the chromosomes.[4] The removal of this protein causes a dramatic loss of the chromosome structure in mitosis, and the cell cycle comes to a stop.[5]

SMC family proteins

Condensin complexes, formed from the union of SMC2 and SMC4 (among other proteins), are responsible for the condensation of chromosomes.[6] Condensin I regulates the timing of chromosome condensation and is essential for changing the chromatin organization at the beginning of mitosis, from TADs to an array of loops around the chromosome axis. Condensin II drives the compaction of the chromosome loops along the axis.[4]

In particular, SMC2 (present in condensin I and II) is detected in the interior of the chromosome as part of the scaffold.[4] When SMC2 is inhibited, the structure of the mitotic chromosome suffers grave defects.[7]

KIF4

KIF4A, a chromokinesin, is implicated in the shaping of chromosomes during mitosis. It binds to condensin I through the CAP-G subunit. It is known that KIF4A regulates the behavior of condensin I, because in absence of KIF4A the chromosome axis does not become enriched with condensin I.[8]

References

  1. 1 2 3 4 5 Poonperm R, Takata H, Hamano T, et al. (2015). "Chromosome Scaffold is a Double-Stranded Assembly of Scaffold Proteins". Scientific Reports. 5: 11916. Bibcode:2015NatSR...511916P. doi:10.1038/srep11916. PMC 4487240. PMID 26132639.
  2. ↑ Paulson JR, Laemmli UK (November 1977). "The structure of histone-depleted metaphase chromosomes". Cell. 12 (3): 817–828. doi:10.1016/0092-8674(77)90280-X. PMID 922894. S2CID 40355379.
  3. ↑ Earnshaw WC, Halligan B, Cooke CA, Heck MM, Liu LF (May 1985). "Topoisomerase II is a structural component of mitotic chromosome scaffolds". Journal of Cell Biology. 100 (5): 1706–1715. doi:10.1083/jcb.100.5.1706. PMC 2113886. PMID 2985625.
  4. 1 2 3 Pollard TD, Earnshaw WC, Lippincott-Schwartz J, Johnson GT (2017). Cell Biology (3rd ed.). Philadelphia: Elsevier. ISBN 978-0-323-34126-4.
  5. ↑ Nielsen CF, Zhang T, Barisic M, Hudson DF (May 2020). "Topoisomerase IIα is essential for maintenance of mitotic chromosome structure". Proceedings of the National Academy of Sciences. 117 (22): 12131–12142. Bibcode:2020PNAS..11712131N. doi:10.1073/pnas.2001760117. PMC 7275761. PMID 32414923.
  6. ↑ Jeppsson K, Kanno T, Shirahige K, Sjögren C (September 2014). "The maintenance of chromosome structure: positioning and functioning of SMC complexes". Nature Reviews Molecular Cell Biology. 15 (9): 601–614. doi:10.1038/nrm3857. PMID 25145851. S2CID 23908801.
  7. ↑ Ono T, Losada A, Hirano M, Myers MP, Neuwald AF, Hirano T (October 2003). "Differential contributions of condensin I and condensin II to mitotic chromosome architecture in vertebrate cells". Cell. 115 (1): 109–121. doi:10.1016/s0092-8674(03)00724-4. PMID 14532007.
  8. ↑ Takahashi M, Wakai T, Hirota T (2016). "Condensin I-mediated mitotic chromosome assembly requires association with chromokinesin KIF4A". Genes & Development. 30 (17): 1931–1936. doi:10.1101/gad.282855.116. PMC 5066236. PMID 27633014.
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