Poster abstracts
Poster number 61 submitted by Chenyu Lin
Pum3 as a molecular player in transcriptional termination and R-Loop-Associated DNA Damage
chenyu Lin (The James Comprehensive Cancer Center, The Ohio State University), Wayne Miles (The James Comprehensive Cancer Center, The Ohio State University)
Abstract:
Pum3 as a molecular player in transcriptional termination and R-Loop-Associated DNA Damage
Pum3 was reported to correlate with resistance to genotoxic exposure ssDNA break via preventing PARP1 degradation by caspase3. Given it is vital for the maintenance of homeostasis that DSBs within transcriptionally active regions undergo accurate repair. However, it remains unknown how Pum3 modulates DSBs response and DNA repair. Our research identified Pum3 as RNA/DNA hybrid interactome that promotes R-loop and transcriptional termination. Pum3 is recruited to the DSB site in a DNA-RNA-hybrid-dependent manner, as playing a critical role in promoting Pol III-mediated R-loop processing and imitating subsequent homologous recombination-mediated repair. Pum3-deficient induces defective HR, accumulation of unrepaired DSBs. Pum3 is overexpressed in PRAD and LIHC cancers, and higher expression of Pum3 correlates with lower survival probability in these cancers. Depletion of Pum3 increases the sensitivity of cancer cells to DNA damage-based therapy-cisplatin. Thus, our data indicated that the function of Pum3 in the presence of R-loops around DSBs within transcriptionally active regions promotes accurate repair of DSBs, which may have implications for cancer therapy.
References:
hPuf-A/KIAA0020 modulates PARP-1 cleavage upon genotoxic stress. (PMID: 21266351)
Keywords: Pum3, R-loop , DNA damage