Chromatin challenges during DNA replication: a systems representation

Abstract

In a recent review, A. Groth and coworkers presented a comprehensive account of nucleosome disassembly in front of a DNA replication fork, assembly behind the replication fork, and the copying of epigenetic information onto the replicated chromatin. Understanding those processes however would be enhanced by a comprehensive graphical depiction analogous to a circuit diagram. Accordingly, we have constructed a molecular interaction map (MIM) that preserves in essentially complete detail the processes described by Groth et al. The MIM organizes and elucidates the information presented by Groth et al. on the complexities of chromatin replication, thereby providing a tool for system-level comprehension of the effects of genetic mutations, altered gene expression, and pharmacologic intervention.

Figure 1.

MIM symbols used in Figure 2 are adapted from Kohn et al. (2006b). The DNA helix unwinding and DNA polymerization symbols are new.

Figure 2.

Molecular interaction map (MIM) of the network that mediates replication of chromatin and its epigenetic modification state, as described by Groth et al. (2007). Each interaction is identified by a number that corresponds to the numbering used in the text and in the Annotations (Appendix 2). The Annotations describe the interactions and give supporting references as cited in Groth et al. (2007). To assist in finding molecular species or interactions on the MIM, a table of coordinates is provided in Appendix 3. The MIM is heuristic, as defined in Kohn et al. (2006a). That means that bindings and/or modifications of a molecular species may exist concurrently (see Figure 1). An interactive electronic version of this MIM can be found at http://discover.nci.nih.gov/mim/index.jsp. (A small filled circle [“node”] on an interaction line represents the molecular species resulting from that interaction; an isolated node represents another copy of the molecular species that is at the other end of the line [Kohn et al., 2006b]. The boxed “2” on the interaction line indicates that two copies of H3:H4 are involved in the binding. The MIM notation rules are summarized in Appendix 1.)