A conserved function for pericentromeric satellite DNA
- University of Michigan, United States
Abstract
A universal and unquestioned characteristic of eukaryotic cells is that the genome is divided into multiple chromosomes and encapsulated in a single nucleus. However, the underlying mechanism to ensure such a configuration is unknown. Here we provide evidence that pericentromeric satellite DNA, which is often regarded as junk, is a critical constituent of the chromosome, allowing the packaging of all chromosomes into a single nucleus. We show that the multi AT-hook satellite DNA binding proteins, D. melanogaster D1 and mouse HMGA1, play an evolutionarily conserved role in bundling pericentromeric satellite DNA from heterologous chromosomes into 'chromocenters', a cytological association of pericentromeric heterochromatin. Defective chromocenter formation leads to micronuclei formation due to budding from the interphase nucleus, DNA damage and cell death. We propose that chromocenter and satellite DNA serves a fundamental role in encapsulating the full complement of the genome within a single nucleus, the universal characteristic of eukaryotic cells.
Article and author information
Author details
Yukiko M Yamashita
Funding
Howard Hughes Medical Institute
- Yukiko M Yamashita
National Institute of General Medical Sciences
- Yukiko M Yamashita
American Heart Association
- Madhav Jagannathan
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Jagannathan et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A conserved function for pericentromeric satellite DNA
eLife 7:e34122.
https://doi.org/10.7554/eLife.34122
Further reading
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- Cell Biology
- Chromosomes and Gene Expression
Structures known as chromocenters, comprising satellite DNA and proteins such as D1 or HMGA1, help to contain DNA inside the nucleus between cell divisions.
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- Cell Biology
- Genetics and Genomics
The six-subunit ORC is essential for the initiation of DNA replication in eukaryotes. Cancer cell lines in culture can survive and replicate DNA replication after genetic inactivation of individual ORC subunits, ORC1, ORC2, or ORC5. In primary cells, ORC1 was dispensable in the mouse liver for endo-reduplication, but this could be explained by the ORC1 homolog, CDC6, substituting for ORC1 to restore functional ORC. Here, we have created mice with a conditional deletion of ORC2, which does not have a homolog. Although mouse embryo fibroblasts require ORC2 for proliferation, mouse hepatocytes synthesize DNA in cell culture and endo-reduplicate in vivo without ORC2. Mouse livers endo-reduplicate after simultaneous deletion of ORC1 and ORC2 both during normal development and after partial hepatectomy. Since endo-reduplication initiates DNA synthesis like normal S phase replication these results unequivocally indicate that primary cells, like cancer cell lines, can load MCM2-7 and initiate replication without ORC.
