S-phase progression in mammalian cells: modelling the influence of nuclear organization

Abstract

The control of DNA replication is of fundamental importance as cell proliferation demands that identical copies of the genetic material are passed to the two daughter cells that form during mitosis. These genetic copies are generated in the preceding S phase, where the entire DNA complement of the mother cell must be copied exactly once. As part of this process, it is known that different regions of mammalian genomes are replicated at specific times of a temporally defined replication programme. The key feature of this programme is that active genes in euchromatin are replicated before inactive ones in heterochromatin. This separation of S phase into periods where different classes of chromatin are duplicated is important in maintaining changes in gene expression that define individual cell types. Recent attempts to understand the structure of the S-phase timing programme have focused on the use of genome-wide strategies that inevitably use DNA isolated from large cell populations for analysis. However, this approach provides a composite view of events that occur within a population without knowledge of the cell-to-cell variability across the population. In this review, we attempt to combine information generated using genome-wide and single cell strategies in order to develop a coherent molecular understanding of S-phase progression. During this integration, we have explored how available information can be introduced into a modelling environment that best describes S-phase progression in mammalian cells.

Nuclear DNA Methylation and Chromatin Condensation Phenotypes Are Distinct Between Normally Proliferating/Aging, Rapidly Growing/Immortal, and Senescent Cells

“…Since this process is meant to mirror the molecular methylation patterns on the replicated strand, it should not change the distribution of methylcytosine within the genome and thus MeC/DAPI codistribution should essentially stay constant. This is in line with the fact that chromatin organization should be conserved during S-phase and inherited to daughter cells upon cell division [94, 97,98]. Therefore the differential methylation phenotypes we observed with 3D-qDMI in this study can be robustly associated with growth behavior and are not skewed by the inherent cell-cycle variability within analyzed cell populations.…”

Cell cycle and lineage progression of neural progenitors in the ventricular-subventricular zones of adult mice

“…It is possible that C cells undergo extensive DNA damage control, extending the T S . Other factors, including slower rate of nucleotides synthesis (61), slower fork elongation during replication (62), or increased heterochromatin (63), could all contribute to a longer T S (64).…”

The BAH domain of BAF180 is required for PCNA ubiquitination

“…3 D and 4 C). Generally, euchromatin DNA is known to be replicated mainly in early S-phase and DNA in heterochromatin is replicated during mid to late S-phase [56]. This might suggest that PCNA ubiquitination occurred less efficiently when the fork is replicating damaged DNA in heterochromatic regions because of its structural complexity, and BAF180 BAH domains might help to decondense the local chromatin structure as we speculated above so that PCNA can be ubiquitinated as well as in the euchromatic regions.…”