Figure 5

Cooperation of the genes in the DNA repair cluster. (A) The matrix shows 51 out of 117 genes in the DNA repair cluster, which belong (marked in red) to eleven known pathways involved in DNA repair (columns; listed on the top). First eight of those pathways are strongly enriched in the cluster (identified using SPIKE [38]). Three other patways (reviewed by Wood et al. [39]) overlap with the cluster, but not significantly (p-values are listed on the bottom). Abbreviations: ATM, ATM pathway; IC, repair of interstrand crosslinks; DSB, repair of double strand breaks; BER, base excision repair; NER, nucleotide excision repair; MR, mismatch repair; G1-S, G1-S pathway; p53, p53 pathway; HR, homologous recombination; PD, polymerase; RAD6, RAD6 pathway. Such strong enrichment in canonical pathways confirms the biological relevance of the deregulated genes in the DNA repair cluster. (B) To identify interconnections between the remaining 66 genes in the cluster, we searched for pathways of length at most one connecting each pair of those genes in a protein-protein and protein-DNA interaction network (using SPIKE and Ingenuity). The resulting graph connects 33 genes (remaining 33 are isolated and not displayed) and represents the complexes to which the genes belong. Some of the complexes are involved in a common process: DNA replication, apoptosis, cell cycle, or telomere maintenance. The network explains connectivity within the DNA repair cluster that goes beyond the canonical pathways.