Significance of Knotted Structures for Function of Proteins and Nucleic Acids
Saturday Abstracts
Single-stranded DNA Topology in Eukaryotes
Zbyszek Otwinowski
, Dominika Borek.
UT Southwestern Medical Center, Dallas, TX, USA.
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.
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