Poster number 1 submitted by Chenyu Lin
PufA regulates R-loop formation, DNA damage repair and chemotherapy resistance
chenyu Lin (The James Comprehensive Cancer Center, The Ohio State University), Jian Ouyang (Massachusetts General Hospital Cancer Center, Harvard Medical School), Eshan Khan (The James Comprehensive Cancer Center, The Ohio State University), Hannah Hylton (The James Comprehensive Cancer Center, The Ohio State University), Lee Zou (Massachusetts General Hospital Cancer Center, Harvard Medical School), Wayne Miles (The James Comprehensive Cancer Center, The Ohio State University)
Double-strand DNA breaks (DSBs) promote the formation of RNA/DNA hybrids (R-loops), as an active mechanism to ensure accurate repair. However, how these RNA/DNA hybrids are formed and protected remains poorly understood. In this study, we identified PufA as a novel regulator of R-loops that are important for R-loops sites that form during transcriptional termination. We find that PufA restricts DNA damage induced by aberrant transcription and also modulates the accumulation of RNA/DNA hybrids at DSBs sites that are required for homologous recombination (HR)-mediated repair. Our data shows that PufA plays an important role in HR-DNA repair and R-loop activity. We find that overexpression of PufA accelerates HR-mediated repair. The loss of PufA leads to the sensitivity of tumor cells to cisplatin, offering new therapeutic opportunities in PufA-deficient tumors.
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Keywords: PufA, R-loop , DNA damage