Next Article in Journal
The Role of Inflammation and Inflammatory Mediators in the Development, Progression, Metastasis, and Chemoresistance of Epithelial Ovarian Cancer
Next Article in Special Issue
p53 Isoforms and Their Implications in Cancer
Previous Article in Journal
Multimodal Radiomic Features for the Predicting Gleason Score of Prostate Cancer
Previous Article in Special Issue
Role of p53 in the Regulation of the Inflammatory Tumor Microenvironment and Tumor Suppression
Article Menu
Issue 8 (August) cover image

Export Article

Open AccessReview
Cancers 2018, 10(8), 250; https://doi.org/10.3390/cancers10080250

The Tip of an Iceberg: Replication-Associated Functions of the Tumor Suppressor p53

1
Fundación Instituto Leloir, Consejo Nacional de Investigaciones Científicas y Técnicas. Av. Patricias Argentinas 435, 1405 Buenos Aires, Argentina
2
Division of Gynecological Oncology, Department of Obstetrics and Gynecology of the University of Ulm, Prittwitzstrasse 43, 89075 Ulm, Germany
*
Authors to whom correspondence should be addressed.
Received: 20 June 2018 / Revised: 16 July 2018 / Accepted: 16 July 2018 / Published: 28 July 2018
(This article belongs to the Special Issue p53 Signaling in Cancers)
Full-Text   |   PDF [1611 KB, uploaded 31 July 2018]   |  

Abstract

The tumor suppressor p53 is a transcriptional factor broadly mutated in cancer. Most inactivating and gain of function mutations disrupt the sequence-specific DNA binding domain, which activates target genes. This is perhaps the main reason why most research has focused on the relevance of such transcriptional activity for the prevention or elimination of cancer cells. Notwithstanding, transcriptional regulation may not be the only mechanism underlying its role in tumor suppression and therapeutic responses. In the past, a direct role of p53 in DNA repair transactions that include the regulation of homologous recombination has been suggested. More recently, the localization of p53 at replication forks has been demonstrated and the effect of p53 on nascent DNA elongation has been explored. While some data sets indicate that the regulation of ongoing replication forks by p53 may be mediated by p53 targets such as MDM2 (murine double minute 2) and polymerase (POL) eta other evidences demonstrate that p53 is capable of controlling DNA replication by directly interacting with the replisome and altering its composition. In addition to discussing such findings, this review will also analyze the impact that p53-mediated control of ongoing DNA replication has on treatment responses and tumor suppressor abilities of this important anti-oncogene. View Full-Text
Keywords: POL iota; POL teta; RAD52; MRE11; ZRANB3; translesion DNA synthesis; template switching; fork reversal; mutant p53; therapy resistance POL iota; POL teta; RAD52; MRE11; ZRANB3; translesion DNA synthesis; template switching; fork reversal; mutant p53; therapy resistance
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Gottifredi, V.; Wiesmüller, L. The Tip of an Iceberg: Replication-Associated Functions of the Tumor Suppressor p53. Cancers 2018, 10, 250.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top