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Your search keyword '"Lisa M. Jenkins"' showing total 2 results
Start Over Author "Lisa M. Jenkins" Journal cell reports
2 results on '"Lisa M. Jenkins"'

1. Long Noncoding RNA PURPL Suppresses Basal p53 Levels and Promotes Tumorigenicity in Colorectal Cancer

Author

Xiao Ling Li, Murugan Subramanian, Matthew F. Jones, Ritu Chaudhary, Deepak K. Singh, Xinying Zong, Berkley Gryder, Sivasish Sindri, Min Mo, Aaron Schetter, Xinyu Wen, Swetha Parvathaneni, Dickran Kazandjian, Lisa M. Jenkins, Wei Tang, Fathi Elloumi, Jennifer L. Martindale, Maite Huarte, Yuelin Zhu, Ana I. Robles, Susan M. Frier, Frank Rigo, Maggie Cam, Stefan Ambs, Sudha Sharma, Curtis C. Harris, Mary Dasso, Kannanganattu V. Prasanth, and Ashish Lal

Subjects
lncRNA, lincRNA, PURPL, p53, HuR, MYBBP1A, LOC643401, LINC01021, RP11-46C20.1, CRC, Biology (General), QH301-705.5
Abstract

Basal p53 levels are tightly suppressed under normal conditions. Disrupting this regulation results in elevated p53 levels to induce cell cycle arrest, apoptosis, and tumor suppression. Here, we report the suppression of basal p53 levels by a nuclear, p53-regulated long noncoding RNA that we termed PURPL (p53 upregulated regulator of p53 levels). Targeted depletion of PURPL in colorectal cancer cells results in elevated basal p53 levels and induces growth defects in cell culture and in mouse xenografts. PURPL associates with MYBBP1A, a protein that binds to and stabilizes p53, and inhibits the formation of the p53-MYBBP1A complex. In the absence of PURPL, MYBBP1A interacts with and stabilizes p53. Silencing MYBBP1A significantly rescues basal p53 levels and proliferation in PURPL-deficient cells, suggesting that MYBBP1A mediates the effect of PURPL in regulating p53. These results reveal a p53-PURPL auto-regulatory feedback loop and demonstrate a role for PURPL in maintaining basal p53 levels.

Published
2017
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2. Resolution of R-loops by topoisomerase III-β (TOP3B) in coordination with the DEAD-box helicase DDX5

Author

Sourav Saha, Xi Yang, Shar-yin Naomi Huang, Keli Agama, Simone Andrea Baechler, Yilun Sun, Hongliang Zhang, Liton Kumar Saha, Shuaikun Su, Lisa M. Jenkins, Weidong Wang, and Yves Pommier

Subjects
DEAD-box RNA Helicases, History, Polymers and Plastics, DNA Topoisomerases, Type I, RNA, Camptothecin, DNA, Business and International Management, R-Loop Structures, Industrial and Manufacturing Engineering, General Biochemistry, Genetics and Molecular Biology
Abstract

The present study demonstrates how TOP3B is involved in resolving R-loops. We observed elevated R-loops in TOP3B knockout cells (TOP3BKO), which are suppressed by TOP3B transfection. R-loop-inducing agents, the topoisomerase I inhibitor camptothecin, and the splicing inhibitor pladienolide-B also induce higher R-loops in TOP3BKO cells. Camptothecin- and pladienolide-B-induced R-loops are concurrent with the induction of TOP3B cleavage complexes (TOP3Bccs). RNA/DNA hybrid IP-western blotting show that TOP3B is physically associated with R-loops. Biochemical assays using recombinant TOP3B and oligonucleotides mimicking R-loops show that TOP3B cleaves the single-stranded DNA displaced by the R-loop RNA-DNA duplex. IP-mass spectrometry and IP-western experiments reveal that TOP3B interacts with the R-loop helicase DDX5 independently of TDRD3. Finally, we demonstrate that DDX5 and TOP3B are epistatic in resolving R-loops in a pathway parallel with senataxin. We propose a decatenation model for R-loop resolution by TOP3B-DDX5 protecting cells from R-loop-induced damage.

Published
2022
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