The Tip of an Iceberg: Replication-Associated Functions of the Tumor Suppressor p53
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 tran...
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-07-01
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| Series: | Cancers |
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| Online Access: | http://www.mdpi.com/2072-6694/10/8/250 |
| _version_ | 1797715337345499136 |
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| author | Vanesa Gottifredi Lisa Wiesmüller |
| author_facet | Vanesa Gottifredi Lisa Wiesmüller |
| author_sort | Vanesa Gottifredi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T08:05:26Z |
| format | Article |
| id | doaj.art-f3d4e00675f34b4a928d25e81b244575 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T08:05:26Z |
| publishDate | 2018-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-f3d4e00675f34b4a928d25e81b2445752023-09-02T19:35:17ZengMDPI AGCancers2072-66942018-07-0110825010.3390/cancers10080250cancers10080250The Tip of an Iceberg: Replication-Associated Functions of the Tumor Suppressor p53Vanesa Gottifredi0Lisa Wiesmüller1Fundación Instituto Leloir, Consejo Nacional de Investigaciones Científicas y Técnicas. Av. Patricias Argentinas 435, 1405 Buenos Aires, ArgentinaDivision of Gynecological Oncology, Department of Obstetrics and Gynecology of the University of Ulm, Prittwitzstrasse 43, 89075 Ulm, GermanyThe 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.http://www.mdpi.com/2072-6694/10/8/250POL iotaPOL tetaRAD52MRE11ZRANB3translesion DNA synthesistemplate switchingfork reversalmutant p53therapy resistance |
| spellingShingle | Vanesa Gottifredi Lisa Wiesmüller The Tip of an Iceberg: Replication-Associated Functions of the Tumor Suppressor p53 Cancers POL iota POL teta RAD52 MRE11 ZRANB3 translesion DNA synthesis template switching fork reversal mutant p53 therapy resistance |
| title | The Tip of an Iceberg: Replication-Associated Functions of the Tumor Suppressor p53 |
| title_full | The Tip of an Iceberg: Replication-Associated Functions of the Tumor Suppressor p53 |
| title_fullStr | The Tip of an Iceberg: Replication-Associated Functions of the Tumor Suppressor p53 |
| title_full_unstemmed | The Tip of an Iceberg: Replication-Associated Functions of the Tumor Suppressor p53 |
| title_short | The Tip of an Iceberg: Replication-Associated Functions of the Tumor Suppressor p53 |
| title_sort | tip of an iceberg replication associated functions of the tumor suppressor p53 |
| topic | POL iota POL teta RAD52 MRE11 ZRANB3 translesion DNA synthesis template switching fork reversal mutant p53 therapy resistance |
| url | http://www.mdpi.com/2072-6694/10/8/250 |
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