Chromosome scaffold

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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]

Contents

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 IIa (green) Chromosome scaffold summary.webp
Immunodetection of a chromosome showing DNA (blue) and two scaffold proteins: SMC2 (red) and topoisomerase IIα (green)

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]

Related Research Articles

<span class="mw-page-title-main">Chromosome</span> DNA molecule containing genetic material of a cell

A chromosome is a package of DNA containing part or all of the genetic material of an organism. In most chromosomes, the very long thin DNA fibers are coated with nucleosome-forming packaging proteins; in eukaryotic cells, the most important of these proteins are the histones. Aided by chaperone proteins, the histones bind to and condense the DNA molecule to maintain its integrity. These eukaryotic chromosomes display a complex three-dimensional structure that has a significant role in transcriptional regulation.

Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in reinforcing the DNA during cell division, preventing DNA damage, and regulating gene expression and DNA replication. During mitosis and meiosis, chromatin facilitates proper segregation of the chromosomes in anaphase; the characteristic shapes of chromosomes visible during this stage are the result of DNA being coiled into highly condensed chromatin.

<span class="mw-page-title-main">Spindle apparatus</span> Feature of biological cell structure

In cell biology, the spindle apparatus is the cytoskeletal structure of eukaryotic cells that forms during cell division to separate sister chromatids between daughter cells. It is referred to as the mitotic spindle during mitosis, a process that produces genetically identical daughter cells, or the meiotic spindle during meiosis, a process that produces gametes with half the number of chromosomes of the parent cell.

<span class="mw-page-title-main">Telophase</span> Final stage of a cell division for eukaryotic cells both in mitosis and meiosis

Telophase is the final stage in both meiosis and mitosis in a eukaryotic cell. During telophase, the effects of prophase and prometaphase are reversed. As chromosomes reach the cell poles, a nuclear envelope is re-assembled around each set of chromatids, the nucleoli reappear, and chromosomes begin to decondense back into the expanded chromatin that is present during interphase. The mitotic spindle is disassembled and remaining spindle microtubules are depolymerized. Telophase accounts for approximately 2% of the cell cycle's duration.

<span class="mw-page-title-main">Condensin</span> Protein complex

Condensins are large protein complexes that play a central role in chromosome assembly and segregation during mitosis and meiosis. Their subunits were originally identified as major components of mitotic chromosomes assembled in Xenopus egg extracts.

<span class="mw-page-title-main">Histone H1</span> Components of chromatin in eukaryotic cells

Histone H1 is one of the five main histone protein families which are components of chromatin in eukaryotic cells. Though highly conserved, it is nevertheless the most variable histone in sequence across species.

<span class="mw-page-title-main">Chromomere</span> Definition of scientific term

A chromomere, also known as an idiomere, is one of the serially aligned beads or granules of a eukaryotic chromosome, resulting from local coiling of a continuous DNA thread. Chromomeres are regions of chromatin that have been compacted through localized contraction. In areas of chromatin with the absence of transcription, condensing of DNA and protein complexes will result in the formation of chromomeres. It is visible on a chromosome during the prophase of meiosis and mitosis. Giant banded (Polytene) chromosomes resulting from the replication of the chromosomes and the synapsis of homologs without cell division is a process called endomitosis. These chromosomes consist of more than 1000 copies of the same chromatid that are aligned and produce alternating dark and light bands when stained. The dark bands are the chromomere.

SMC complexes represent a large family of ATPases that participate in many aspects of higher-order chromosome organization and dynamics. SMC stands for Structural Maintenance of Chromosomes.

Eukaryotic chromosome structure refers to the levels of packaging from raw DNA molecules to the chromosomal structures seen during metaphase in mitosis or meiosis. Chromosomes contain long strands of DNA containing genetic information. Compared to prokaryotic chromosomes, eukaryotic chromosomes are much larger in size and are linear chromosomes. Eukaryotic chromosomes are also stored in the cell nucleus, while chromosomes of prokaryotic cells are not stored in a nucleus. Eukaryotic chromosomes require a higher level of packaging to condense the DNA molecules into the cell nucleus because of the larger amount of DNA. This level of packaging includes the wrapping of DNA around proteins called histones in order to form condensed nucleosomes.

In chromatin, those proteins which remain after the histones have been removed, are classified as non-histone proteins. The non-histone proteins, are a large group of heterogeneous proteins that play a role in organization and compaction of the chromosome into higher order structures. They play vital roles in regulating processes like nucleosome remodeling, DNA replication, RNA synthesis and processing, nuclear transport, steroid hormone action and interphase/mitosis transition. Scaffold proteins, DNA polymerase, Heterochromatin Protein 1 and Polycomb are common non-histone proteins. This classification group also includes numerous other structural, regulatory, and motor proteins. Non-histone protein are acidic.

<span class="mw-page-title-main">Aurora kinase B</span> Protein

Aurora kinase B is a protein that functions in the attachment of the mitotic spindle to the centromere and in cytokinesis.

<span class="mw-page-title-main">KIF4A</span> Protein-coding gene in the species Homo sapiens

Kinesin family member 4A is a protein that in humans is encoded by the KIF4A gene.

<span class="mw-page-title-main">SMC4</span> Protein-coding gene in the species Homo sapiens

Structural maintenance of chromosomes protein 4 (SMC-4) also known as chromosome-associated polypeptide C (CAP-C) or XCAP-C homolog is a protein that in humans is encoded by the SMC4 gene. SMC-4 is a core subunit of condensin I and II, large protein complexes involved in high order chromosome organization, including condensation and segregation. SMC-4 protein is commonly associated with the SMC-2 protein, another protein complex within the SMC protein family. SMC-4 dimerizes with SMC-2, creating the flexible and dynamic structure of the condensin holocomplex. An over-expression of the SMC-4 protein is shown to impact carcinogenesis.

<span class="mw-page-title-main">NCAPD2</span> Protein-coding gene in the species Homo sapiens

Condensin complex subunit 1 also known as chromosome-associated protein D2 (CAP-D2) or non-SMC condensin I complex subunit D2 (NCAPD2) or XCAP-D2 homolog is a protein that in humans is encoded by the NCAPD2 gene. CAP-D2 is a subunit of condensin I, a large protein complex involved in chromosome condensation.

<span class="mw-page-title-main">NCAPH</span> Protein-coding gene in the species Homo sapiens

Condensin complex subunit 2 also known as chromosome-associated protein H (CAP-H) or non-SMC condensin I complex subunit H (NCAPH) is a protein that in humans is encoded by the NCAPH gene. CAP-H is a subunit of condensin I, a large protein complex involved in chromosome condensation. Abnormal expression of NCAPH may be linked to various types of carcinogenesis as a prognostic indicator.

<span class="mw-page-title-main">SMC2</span> Protein-coding gene in the species Homo sapiens

Structural maintenance of chromosomes protein 2 (SMC-2), also known as chromosome-associated protein E (CAP-E), is a protein that in humans is encoded by the SMC2 gene. SMC2 is part of the SMC protein family and is a core subunit of condensin I and II, large protein complexes involved in chromosome condensation, overall organization. Several studies have demonstrated the necessity of SMC2 for cell division and proliferation.

<span class="mw-page-title-main">DNA condensation</span>

DNA condensation refers to the process of compacting DNA molecules in vitro or in vivo. Mechanistic details of DNA packing are essential for its functioning in the process of gene regulation in living systems. Condensed DNA often has surprising properties, which one would not predict from classical concepts of dilute solutions. Therefore, DNA condensation in vitro serves as a model system for many processes of physics, biochemistry and biology. In addition, DNA condensation has many potential applications in medicine and biotechnology.

<span class="mw-page-title-main">Scaffold/matrix attachment region</span>

The term S/MAR, otherwise called SAR, or MAR, are sequences in the DNA of eukaryotic chromosomes where the nuclear matrix attaches. As architectural DNA components that organize the genome of eukaryotes into functional units within the cell nucleus, S/MARs mediate structural organization of the chromatin within the nucleus. These elements constitute anchor points of the DNA for the chromatin scaffold and serve to organize the chromatin into structural domains. Studies on individual genes led to the conclusion that the dynamic and complex organization of the chromatin mediated by S/MAR elements plays an important role in the regulation of gene expression.

William Charles Earnshaw is an American biologist who is Professor of Chromosome Dynamics at the University of Edinburgh, where he has been a Wellcome Trust Principal Research Fellow since 1996.

Xenopus egg extract is a lysate that is prepared by crushing the eggs of the African clawed frog Xenopus laevis. It offers a powerful cell-free system for studying various cell biological processes, including cell cycle progression, nuclear transport, DNA replication and chromosome segregation. It is also called Xenopus egg cell-free system or Xenopus egg cell-free extract.

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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