Short abstract (50 words)
We show the results of our effort to describe interactions among the network of proteins
that participate in the intra-S checkpoint response to DNA damage, and the motif
structure of the intra-S checkpoint proteome. We also demonstrate a new tool to visualize
a hierarchical cluster tree of proteins.
Long abstract (250 words)
One goal of systems biology is to determine the biological significance of myriad
interactions among cell proteins. High-through tools have used two-hybrid analysis to
determine interactions among all of the S. cerevisiae open-reading frames. Similar efforts
are underway to define protein interaction networks in humans and other vertebrate and
invertebrate species. We show here the results of our effort to describe interactions
among the network of proteins that participate in the intra-S checkpoint response to DNA
damage. DNA damage checkpoint sense alterations in DNA structure and signal to the
machinery of cell cycle to arrest or delay phase transitions. The intra-S checkpoint
recognizes stalled DNA replication forks and sends signals to delay initiation of latefiring replicons and slow the rate of chain elongation by DNA polymerases. We have
identified a set of 30 gene products that contribute to intra-S checkpoint response in
human cells. Using the IDEA (idea.renci.org) website developed by RENCI and NCSA,
we determined the yeast homologues of these human genes, created and visualized maps
of the network of protein interactions in the human intra-S checkpoint using the opensource Cytoscape visualization tool. Protein interactions as demonstrated by two-hybrid
analysis or co-immunoprecipitation are determined by specific domains of motifs that
interact. The Motif-Network tool being created by RENCI and NCSA scientists enables
researchers to determine the motifs that are represented in selected proteomes. Proteins
that share motifs may share binding partners and biological functions. We show the motif
structure of the intra-S checkpoint proteome.