Genetic Stabilization by P53 Involves Growth Regulatory and Repair Pathways

Overview

Journal J Biomed Biotechnol

Specialty Biology

Date 2002 Dec 19

PMID 12488620

Citations 4

Authors

Lisa Wiesmuller

Affiliations

Soon will be listed here.

Abstract

p53 performs a plethora of activities, which are directed towards the maintenance of the genomic integrity and constitute its universal role as a tumor suppressor. 1000 to 10000 latent p53 molecules are permanently available in order to monitor DNA exchange processes in mitotically growing cells. After the introduction of major DNA injuries the levels of posttranslationally modified p53 proteins rise, which in turn transcriptionally signal transient cell cycle arrest or apoptotic cell death, depending on the extent of damage. Taken together, p53 inhibits the manifestation of genomic instabilities at different control levels both during naturally occurring metabolic processes and in response to genotoxic treatments.

Citing Articles

Classification of TP53 mutations and HPV predict survival in advanced larynx cancer.

Scheel A, Bellile E, McHugh J, Walline H, Prince M, Urba S Laryngoscope. 2016; 126(9):E292-9.

PMID: 27345657 PMC: 5002993. DOI: 10.1002/lary.25915.

More targets, more pathways and more clues for mutant p53.

Garritano S, Inga A, Gemignani F, Landi S Oncogenesis. 2013; 2:e54.

PMID: 23817466 PMC: 3740285. DOI: 10.1038/oncsis.2013.15.

TP53 status and response to treatment in breast cancers.

Varna M, Bousquet G, Plassa L, Bertheau P, Janin A J Biomed Biotechnol. 2011; 2011:284584.

PMID: 21760703 PMC: 3114547. DOI: 10.1155/2011/284584.

Recombinational DNA Repair in Cancer and Normal Cells: The Challenge of Functional Analysis.

Willers H, Xia F, Powell S J Biomed Biotechnol. 2002; 2(2):86-93.

PMID: 12488588 PMC: 153788. DOI: 10.1155/S1110724302204027.

References

McGill G, Fisher D . p53 and cancer therapy: a double-edged sword. J Clin Invest. 1999; 104(3):223-5. PMC: 408427. DOI: 10.1172/JCI7861. View

Oberosler P, Hloch P, Ramsperger U, Stahl H . p53-catalyzed annealing of complementary single-stranded nucleic acids. EMBO J. 1993; 12(6):2389-96. PMC: 413469. DOI: 10.1002/j.1460-2075.1993.tb05893.x. View

Xia S, Shammas M, Shmookler Reis R . Elevated recombination in immortal human cells is mediated by HsRAD51 recombinase. Mol Cell Biol. 1997; 17(12):7151-8. PMC: 232572. DOI: 10.1128/MCB.17.12.7151. View

Huang P . Excision of mismatched nucleotides from DNA: a potential mechanism for enhancing DNA replication fidelity by the wild-type p53 protein. Oncogene. 1998; 17(3):261-70. DOI: 10.1038/sj.onc.1201946. View

Komarov P, Komarova E, Kondratov R, Coon J, Chernov M, Gudkov A . A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy. Science. 1999; 285(5434):1733-7. DOI: 10.1126/science.285.5434.1733. View

Lane D . Cancer. p53, guardian of the genome. Nature. 1992; 358(6381):15-6. DOI: 10.1038/358015a0. View

Kearsey J, Coates P, Prescott A, Warbrick E, Hall P . Gadd45 is a nuclear cell cycle regulated protein which interacts with p21Cip1. Oncogene. 1995; 11(9):1675-83. View

Gowen L, Avrutskaya A, Latour A, Koller B, Leadon S . BRCA1 required for transcription-coupled repair of oxidative DNA damage. Science. 1998; 281(5379):1009-12. DOI: 10.1126/science.281.5379.1009. View

Kearsey J, Shivji M, Hall P, Wood R . Does the p53 up-regulated Gadd45 protein have a role in excision repair?. Science. 1995; 270(5238):1004-5; author reply 1005-6. View

10.

Blander G, Kipnis J, Leal J, Yu C, Schellenberg G, Oren M . Physical and functional interaction between p53 and the Werner's syndrome protein. J Biol Chem. 1999; 274(41):29463-9. DOI: 10.1074/jbc.274.41.29463. View

11.

Levine A . p53, the cellular gatekeeper for growth and division. Cell. 1997; 88(3):323-31. DOI: 10.1016/s0092-8674(00)81871-1. View

12.

Lane D . Awakening angels. Nature. 1998; 394(6694):616-7. DOI: 10.1038/29166. View

13.

Sherr C . Tumor surveillance via the ARF-p53 pathway. Genes Dev. 1998; 12(19):2984-91. DOI: 10.1101/gad.12.19.2984. View

14.

Wang X, Ohnishi K, Takahashi A, Ohnishi T . Poly(ADP-ribosyl)ation is required for p53-dependent signal transduction induced by radiation. Oncogene. 1999; 17(22):2819-25. DOI: 10.1038/sj.onc.1202216. View

15.

Smith M, Chen I, Zhan Q, Bae I, Chen C, Gilmer T . Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen. Science. 1994; 266(5189):1376-80. DOI: 10.1126/science.7973727. View

16.

Ishizaki K, Ejima Y, Matsunaga T, Hara R, Sakamoto A, Ikenaga M . Increased UV-induced SCEs but normal repair of DNA damage in p53-deficient mouse cells. Int J Cancer. 1994; 58(2):254-7. DOI: 10.1002/ijc.2910580218. View

17.

Nelson W, Kastan M . DNA strand breaks: the DNA template alterations that trigger p53-dependent DNA damage response pathways. Mol Cell Biol. 1994; 14(3):1815-23. PMC: 358539. DOI: 10.1128/mcb.14.3.1815-1823.1994. View

18.

Bunz F, Dutriaux A, Lengauer C, Waldman T, Zhou S, Brown J . Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science. 1998; 282(5393):1497-501. DOI: 10.1126/science.282.5393.1497. View

19.

Patel K, Yu V, Lee H, Corcoran A, Thistlethwaite F, Evans M . Involvement of Brca2 in DNA repair. Mol Cell. 1998; 1(3):347-57. DOI: 10.1016/s1097-2765(00)80035-0. View

20.

Kazantsev A, Sancar A . Does the p53 up-regulated Gadd45 protein have a role in excision repair?. Science. 1995; 270(5238):1003-4; author reply 1005-6. View