Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/89990
Title: P53 maintains genomic stability by preventing interference between transcription and replication
Authors: Yeo, Constance Qiao Xin
Alexander, Irina
Lin, Zhaoru
Lim, Shuhui
Aning, Obed Akwasi
Kumar, Ramesh
Sangthongpitag, Kanda
Pendharkar, Vishal
Ho, Vincent H.B.
Cheok, Chit Fang
Keywords: Gyrase Inhibitor
Protein p53
DRNTU::Science::Medicine
Issue Date: 2016
Source: Yeo, C. Q. X., Alexander, I., Lin, Z., Lim, S., Aning, O. A., Kumar, R., . . . Cheok, C. F. (2016). p53 Maintains Genomic Stability by Preventing Interference between Transcription and Replication. Cell Reports, 15(1), 132-146. doi:10.1016/j.celrep.2016.03.011
Series/Report no.: Cell Reports
Abstract: p53 tumor suppressor maintains genomic stability, typically acting through cell-cycle arrest, senescence, and apoptosis. We discovered a function of p53 in preventing conflicts between transcription and replication, independent of its canonical roles. p53 deficiency sensitizes cells to Topoisomerase (Topo) II inhibitors, resulting in DNA damage arising spontaneously during replication. Topoisomerase IIα (TOP2A)-DNA complexes preferentially accumulate in isogenic p53 mutant or knockout cells, reflecting an increased recruitment of TOP2A to regulate DNA topology. We propose that p53 acts to prevent DNA topological stress originating from transcription during the S phase and, therefore, promotes normal replication fork progression. Consequently, replication fork progression is impaired in the absence of p53, which is reversed by transcription inhibition. Pharmacologic inhibition of transcription also attenuates DNA damage and decreases Topo-II-DNA complexes, restoring cell viability in p53-deficient cells. Together, our results demonstrate a function of p53 that may underlie its role in tumor suppression.
URI: https://hdl.handle.net/10356/89990
http://hdl.handle.net/10220/46473
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2016.03.011
Rights: © 2016 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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