The p53 family of transcription factors (p53,p63,p73) function as tumour suppressors by promoting apoptosis, cell cycle arrest and DNA repair. Recent studies revealed that p63 and p73 promote DNA repair by transcriptionally activating components of the Fanconi anemia (FA) repair network. In addition, dominant negative isoforms of p63 are frequently upregulated in head and neck squamous cell carcinomas (HNSCC), a tumor most FA adult survivors eventually develop. Thus, understanding how p63 promotes DNA repair and genome stability will help elucidate the molecular basis of FA and facilitate development of therapies for HNSCC in FA patients. The presence of multiple paralogues and isoforms with overlapping functions complicate analysis of the p53 family in vertebrates. The nematode Caenorhabditis elegans contains a single p53 family member (CEP-1) and most of the FA repair network proteins. Structurally, CEP-1 is more similar to p63/p73 than p53 and gene profiling studies showed considerable overlap between the targets of CEP-1 and human p63. Recent work in our lab revealed that CEP-1 has a minor role in promoting meiotic recombination and DNA interstrand crosslink (ICL) repair that is similar to several FA genes, but defects in these processes are significantly enhanced when cep-1 is co-ablated with these FA genes. These preliminary results suggest that CEP-1 cooperates in parallel with the FA proteins to promote meiosis and ICL repair. During my PhD studies, I will define the mechanism by which CEP-1 collaborates with the FA network to promote ICL repair using the powerful genetics and in vivo imaging tools available in C. elegans. I will translate my findings in C. elegans to mammalian models to ask whether p63 has conserved interactions with the FA network in promoting ICL repair. My work on CEP-1/p63 will provide new insights into the DNA repair defects of FA and ideally uncover new therapeutic targets for the treatment and prevention of FA-associated phenotypes.