Medical Molecular Biology Commons^™

Elevated Paf1-Rad52 Axis Confers Chemoresistance To Human Cancers, Sanchita Rauth, Koelina Ganguly, Pranita Atri, Seema Parte, Rama Krishna Nimmakayala, Venkatesh Varadharaj, Palanisamy Nallasamy, Raghupathy Vengoji, Ayoola O. Ogunleye, Imayavaramban Lakshmanan, Ramakanth Chirravuri, Mika Bessho, Jesse L. Cox, Jason M. Foster, Geoffrey A. Talmon, Tadayoshi Bessho, Apar Kishor Ganti, Surinder K. Batra, Moorthy P. Ponnusamy

Journal Articles: Biochemistry & Molecular Biology

Cisplatin- and gemcitabine-based chemotherapeutics represent a mainstay of cancer therapy for most solid tumors; however, resistance limits their curative potential. Here, we identify RNA polymerase II-associated factor 1 (PAF1) as a common driver of cisplatin and gemcitabine resistance in human cancers (ovarian, lung, and pancreas). Mechanistically, cisplatin- and gemcitabine-resistant cells show enhanced DNA repair, which is inhibited by PAF1 silencing. We demonstrate an increased interaction of PAF1 with RAD52 in resistant cells. Targeting the PAF1 and RAD52 axis combined with cisplatin or gemcitabine strongly diminishes the survival potential of resistant cells. Overall, this study shows clinical evidence that the expression …