Editing DNA replication (section)

==== Replication focus ====
In vertebrate cells, replication sites concentrate into positions called '''replication foci'''.<ref name="in&out" /> Replication sites can be detected by immunostaining daughter strands and replication enzymes and monitoring GFP-tagged replication factors. By these methods it is found that replication foci of varying size and positions appear in S phase of cell division and their number per nucleus is far smaller than the number of genomic replication forks.

'''P. Heun et al.''',<ref name="in&out" />(2001) tracked GFP-tagged replication foci in budding yeast cells and revealed that replication origins move constantly in G1 and S phase and the [[Molecular dynamics|dynamics]] decreased significantly in S phase.<ref name="in&out" /> Traditionally, replication sites were fixed on spatial structure of chromosomes by [[nuclear matrix]] or [[lamin]]s. The Heun's results denied the traditional concepts, budding yeasts do not have lamins, and support that replication origins self-assemble and form replication foci.{{cn|date=November 2024}}

By firing of replication origins, controlled spatially and temporally, the formation of replication foci is regulated. D. A. Jackson et al.(1998) revealed that neighboring origins fire simultaneously in mammalian cells.<ref name="in&out" /> Spatial juxtaposition of replication sites brings '''clustering''' of replication forks. The clustering do '''rescue of stalled replication forks''' and favors normal progress of replication forks. Progress of replication forks is inhibited by many factors; collision with proteins or with complexes binding strongly on DNA, deficiency of dNTPs, nicks on template DNAs and so on. If replication forks get stuck and the rest of the sequences from the stuck forks are not copied, then the daughter strands get nick nick unreplicated sites. The un-replicated sites on one parent's strand hold the other strand together but not daughter strands. Therefore, the resulting sister chromatids cannot separate from each other and cannot divide into 2 daughter cells. When neighboring origins fire and a fork from one origin is stalled, fork from other origin access on an opposite direction of the stalled fork and duplicate the un-replicated sites. As other mechanism of the rescue there is application of '''dormant replication origins''' that excess origins do not fire in normal DNA replication.{{cn|date=November 2024}}