IRF1 and the DNA damage response: Friend or foe

4^th World Congress on Cancer Science & Therapy

October 20-22, 2014 DoubleTree by Hilton Hotel Chicago-North Shore Conference Center, USA

Nicole Clarke

Accepted Abstracts: J Cancer Sci Ther

Abstract :

Interferon regulatory factor-1 (IRF-1) is an important anti-oncogenic transcription factor. A key component of IRF-1?s tumor suppressor activity is the induction of apoptosis in cancer cells and many of its? gene targets are involved in the extrinsic or intrinsic apoptotic pathways. Early studies showed that IRF1 was also involved in DNA damage responses. IRF1 regulates DNA damage-induced apoptosis and cell cycle arrest but the target genes responsible for it?s? activity were not known. Genomewide studies, ChIP-chip and ChIP-Sequencing identified a number of gene targets of IRF1 within the DNA damage response including, BRIP1/FANCJ, FANCF, PCNA, and ATR (Ataxia telangiectasia and Rad3 related) signaling components. Fanconi anemia (FA) proteins like FANCJ and ATR signaling proteins play a role in DNA interstrand crosslink repair (ICL). Our previous work has shown that IRF1 is involved in the DNA damage response to ICLs, as cells deficient in IRF1 protein display a similar phenotype to Fanconi anemia (FA) deficient cells, increased accumulation in G2/M. The transcriptional regulation of DNA damage repair proteins such as BRIP1/FANCJ or other ATR signaling proteins most likely contributes to IRF1?s role in this response. In addition, DNA motif discovery identified a set of significantly enriched IRF1 bound DNA sequences at the promoters of DNA damage genes. Furthermore, functional characterization of the IRF1 bound genes identified by ChIP-Seq demonstrated that the major gene target pathway of IRF1 is apoptosis. These data will impact on our understanding of antioncogenic pathways in cells and how IRF1 may contribute to the response to chemotherapeutic drugs.

Biography :

Nicole Clarke completed her PhD in Molecular and Cellular Biology from Columbia University and Postdoctoral studies at the Institut de Génétique et de Biologie Moléculaire et Cellulaire. Her research work is focused on elucidating tumor suppressor networks in cells and understanding how these pathways are affected by novel protein-protein interactions and posttranslational modifications. She has published in international journals and serves as an Editorial Board Member for ISRN International Scholarly Research Notices.