Mechanism of G1 Radiation Checkpoint Activation Figure 2. Hit gene-ontology and pathway associations. A) Pathway representation within hit pool. Hits were analysed for pathway association using the DAVID functional annotation tool (http://david.abcc.ncifcrf.gov/). B) Enrichment for gene ontology. Pathway association was analysed for hits and input using DAVID. Pathway representation within hits is plotted against that for input targets. C) Hit validation. Hits were assessed using individual oligonucleotides represented within the pool. The number of active oligonucleotides and level of response is indicated. Hit classification was as for the screen. doi:10.1371/journal.pone.0031627.g002 irradiation of cells induces expression of p21CIP1/WAF1 [41], and the cyclin-dependent kinases (CDKs) responsible for phosphory- lation of RB1 are inhibited by p21CIP1/WAF1 [42,43,44] providing a potential mechanism by which IR treatment leads to the accumulation of active RB1 in cells. Our results that siRNA targeting p21CIP1/WAF1 leads to radiation-resistant RB1 phos- PLoS ONE | www.plosone.org 4 February 2012 | Volume 7 | Issue 2 | e31627