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Single-stranded DNA topology in Eukaryotes
by
Zbyszek Otwinowski
UT Southestern Medical Center
Coauthors: Dominika Borek
In a single chromosome, both template strands are wrapped around each other and become replicated at hundreds of
sites in parallel to form new dsDNA molecules, which are subsequently individualized into sister chromatids in prophase and
segregated to daughter cells later in anaphase. How the entanglement is avoided during individualization remains unclear. The
replication of holocentric and ring chromosomes provides much insight into this process. The products of replication do not
become entangled during mitosis for either chromosome type, and this indicates that during replication the template strands are
differentiated in a coordinated manner. Additionally, patterns of labeling in diplochromosomes that are created during
endoreduplication show that this mechanism relies on the memory of DNA strands formation, i.e. information about the order in
which two strands have been replicated is propagated across generations. Because information that differentiates strands in
dsDNA, is passed on from one generation to the next one, the mechanism of this process is by definition epigenetic.
We propose a mechanism of coordinated strand recognition that relies on formation of single-stranded topological structures,
which are generated during DNA synthesis. Structures of such type, called hemicatenanes, have been observed in plasmids,
viruses and Crenarchaeota the prokaryotes with the replication mechanism most closely related to that of eukaryotes.
Topological structures based on single-stranded DNA are likely to be a missing element that hinders our understanding of: (1)
the differentiation of the sister chromatids during their individualization, (2) the formation of higher-order structures in mitotic
chromosomes coupled to individualization, (3) ORI definition, (4) cis-regulation in epigenetic processes and (5) asymmetric cell
division, (6) spatial, temporal, and genomic co-linearity of transcriptional programs that control developmental processes.
Date received: December 15, 2014
Copyright © 2014 by the author(s). The author(s) of this work and the organizers of the conference have granted their consent to include this abstract in Topology Atlas. Document # cbjz-57.