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Research Paper

Metakaryotic stem cell nuclei use pangenomic dsRNA/DNA intermediates in genome replication and segregation

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Pages 44-52 | Received 10 Jul 2013, Accepted 30 Dec 2013, Published online: 13 Jan 2014
 

Abstract

Bell shaped nuclei of metakaryotic cells double their DNA content during and after symmetric and asymmetric amitotic fissions rather than in the separate, pre-mitotic S-phase of eukaryotic cells. A parsimonious hypothesis was tested that the two anti-parallel strands of each chromatid DNA helix were first segregated as ssDNA-containing complexes into sister nuclei then copied to recreate a dsDNA genome. Metakaryotic nuclei that were treated during amitosis with RNase A and stained with acridine orange or fluorescent antibody to ssDNA revealed large amounts of ssDNA. Without RNase treatment metakaryotic nuclei in amitosis stained strongly with an antibody complex specific to dsRNA/DNA. Images of amitotic figures co-stained with dsRNA/DNA antibody and DAPI indicated that the entire interphase dsDNA genome (B-form helices) was transformed into two dsRNA/DNA genomes (A-form helices) that were segregated in the daughter cell nuclei then retransformed into dsDNA. As this process segregates DNA strands of opposite polarity in sister cells it hypothetically offers a sequential switching mechanism within the diverging stem cell lineages of development.

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

These efforts were supported initially by personal funds (Gostjeva EV, Thilly WG) and internal funds of the Leiden University Medical Centre (Fomina JN, Darroudi F). Three of us (Gostjeva EV, Thilly WG, Koledova VV) have been supported at MIT since 2007 by a research contract to study metakaryotic phenomena in human diseases from the United Therapeutics Corporation of Silver Spring, MD, USA. We acknowledge useful scientific discussions with Drs Martine Rothblatt, Mary Smith (United Therapeutics), Ray Kurzweil and Aaron Kleiner (Kurzweil Technologies, Wellesley, MA, USA), Christopher F Nicodemus (AIT Strategies, Franconia, NH, USA), Dr James L Sherley (The Adult Stem Cell Technolgy Center, LLC, Boston, MA, USA), Prof Kari Hemminki, Deutsch Zentrum fur Krebs Forschung, Heidelberg, Germany and the late Prof David Schauer (MIT).