The initiation of DNA replication involves the formation
of multiple protein complexes and a series of regulatory process
mediating the intaraction of these complexes with each other.
The predominant molecular interactions are altered at different
stages of the cell cycle and respond to DNA damage and potentially
genotoxic condition. In this work, we summarize the events leading to
initiation of DNA replication as a molecular interaction map,
a concise way to describe the interactions between molecules
that are involved in a particular biochemical pathway.
The maps describe the various ways by which cells regulate DNA replication,
and in particular, prevent the initiation of DNA synthesis under condizion
that may perturb replication and affect genomic stability.
|How to read the maps
In the molecular interaction map, each named molecule is shown
only in one location. A variety of defined connecting lines serve
to describe the interactions between the molecules.We depict binary
interactions by means of a variety of line types, distinguished by different
types of arrowheads placed at the end of the line. We depict multimolecular
complexes or modified forms by means of "nodes" placed on the lines.
The line-types and node definitions are summarized in this figure.
A line may originate either at a named molecular species or at a node,
and may terminate at a named species, a node, or at another line.
When lines cross, no interaction between them is implied. A node placed
within a line (not at the ends) represents the consequence of the implied
binary interaction. When a line indicates reversible binding, a node within
the line represents the complex formed by the combination of the species
defined at the ends of the line. When the line indicates modification of a
protein, a node within the line represents the modified protein itself.
This notation is extensible, since a node represents a molecular species,
which can be connected to other species by means of interaction lines.
In this way, multimolecular complexes can be built up. For convenience and
clarity, multiple nodes may be placed whithin the same line; these nodes
then refer to exactly the same thing. A node should not appear at the
intersection between lines when this would create an ambiguity.
Covalent modification of a protein is represented by a line having
a barbed arrowhead pointing to the site of modification, while the other
end of the line, at which the type of modification (e.g. phosphorylation)
is indicated, has no arrowhead. A node placed on the line denotes the modified
protein itself. A reaction or conversion in which one or more species
(e.g. reaction products) are generated while other species (e.g. reactants)
are stoichiometrically consumed is denoted by solid arrowhead, as
shown in the summary of symbols. The same symbology can be used to
represent the transport of molecula species from one compartment in
the cell to another, since this is essentially a stoichiometric
appearence and disappearence of molecules in different places.
Stimulation of a process is represented by an open triangle arrowhead
if the stimulatory element is necessary for the process,
then a bar is added behind the open triangle arrowhead.
Inibitory effects are denoted by a bar at the end of the line.
This web site present an interactive version of these molecular interaction maps.
To reach an annotation for a particular molecular interaction,
click on the imitation number within the maps.
Clicking on the numbers we open a popup where we can find the annotation text
and the corrispondence references cited in the text.
Clicking on the refences we open the PubMed page of the reference. To reach the
description of each protein, click on the "cartouche". We'll open a popup where we
can find also links to related databases.
To toggle between S phase, mitosis, DNA damage and replication inhibition maps,
click on the navigation bar above the header.