Abstract
Reactive oxygen species (ROS) cause DNA double-strand or single-strand breaks. ROS form one of the main causes of DNA damage. Environmental factors as well as host factors increase ROS. The volatile sulfur compounds in the oral cavity, especially oral malodorous compounds, are the most probable producers of ROS. The functions of p53 involve causing p53-dependent apoptosis, repairing DNA-strand errors and arresting the cell cycle for DNA repair. A signal network reacting to DNA or genomic damage selects either apoptosis or the repair of DNA breaks after the cellular DNA or genome is damaged. The network involves the checkpoints: p53, Ataxia-telangiectasia and Rad3-related (ATR), and Ataxia-telangiectasia mutated (ATM) protein kinase have important roles. The signal network works together with the cell cycle. Checkpoints in the network hold the cell cycle at a certain point. Genotoxicity, in which checkpoint kinase 1 and 2 also have important roles, controls the network, including the checkpoints, indirectly. There are three groups of checkpoints: cell-cycle checkpoints (DNA-damage checkpoints), DNA-replication checkpoints, and the spindle checkpoint. These checkpoints detect DNA damage and then promote either DNA repair or cell death. Because of this system the cell preserves genomic integrity. In other words, the cell and/or the host can eliminate genomic error from the host.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Enoch T, Norbury C (1995) Cellular responses to DNA damage: cell-cycle checkpoints, apoptosis and the roles of p53 and ATM. Trends Biochem Sci 20:426–430
Meyn MS (1995) Ataxia-telangiectasia and cellular responses to DNA damage. Cancer Res 55:5991–6001
Meyn MS (1997) Ataxia-telangiectasia and cellular responses to DNA damage. Cancer Res 57:2313–2315
Aoyama I, Calenic B, Imai T et al (2012) Oral malodorous compound causes caspase-8 and -9 mediated programmed cell death in osteoblasts. J Periodontal Res 47:365–373
Calenic B, Yaegaki K, Ishkitiev N et al (2012) p53-Pathway activity and apoptosis in hydrogen sulfide-exposed stem cells separated from human gingival epithelium. J Periodontal Res. doi:10.1111/jre.12011
Calenic C, Yaegaki K, Kozhuharova A et al (2010) Oral malodorous compound causes oxidative stress and p53-mediated programmed cell death in keratinocyte stem cells. J Periodontol 81:1317–1323
Calenic B, Yaegaki K, Murata T et al (2010) Oral malodorous compound triggers mitochondrial-dependent apoptosis and causes genomic DNA damage in human gingival epithelial cells. J Periodontal Res 45:31–37
Kobayashi C, Yaegaki K, Calenic B et al (2011) Hydrogen sulfide causes apoptosis in human pulp stem cells. J Endod 37:479–484
Fujimura M, Calenic B, Yaegaki K et al (2010) Oral mal odorous compound activates mitochondrial pathway inducing apoptosis in human gingival fibroblasts. Clin Oral Investig 14(367–373):2010
Yaegaki K, Qian W, Murata T et al (2008) Oral malodorous compound causes apoptosis and genomic DNA damage in human gingival fibroblasts. J Periodontal Res 43:391–399
Bellini MF, Cadamuro AC, Succi M et al (2012) Alterations of the TP53 gene in gastric and esophageal carcinogenesis. J Biomed Biotechnol 2012:891961
Lane DP (1992) p53, guardian of the genome. Nature 358:15–16
Sato Y, Tsurumi T (2012) Genome guardian p53 and viral infections. Rev Med Virol. doi:10.1002/rmv.1738
Todd R, Hinds PW, Munger K et al (2002) Cell cycle dysregulation in oral cancer. Crit Rev Oral Biol Med 13:51–61
Trenz K, Smith E, Smith S et al (2006) ATM and ATR promote Mre11 dependent restart of collapsed replication forks and prevent accumulation of DNA breaks. EMBO J 25:1764–1774
Langerak P, Russell P (2011) Regulatory networks integrating cell cycle control with DNA damage checkpoints and double-strand break repair. Philos Trans R Soc Lond B Biol Sci 366:3562–3571
Landau DA, Slack FJ (2011) MicroRNAs in mutagenesis, genomic instability and DNA repair. Semin Oncol 38:743–751
Tian B, Yang Q, Mao Z (2009) Phosphorylation of ATM by Cdk5 mediates DNA damage signaling and regulates neuronal death. Nat Cell Biol 11:211–218
Kinner A, Wu W, Staudt C et al (2008) c-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin. Nucleic Acids Res 36:5678–5694
Lau AW, Fukushima H, Wei W (2011) The Fbw7 and beta-TRCP E3 ubiquitin ligases and their roles in tumorigenesis. Front Biosci 17:2197–2212
Doorbar J (2005) The papillomavirus life cycle. J Clin Virol 32S:S7–S15
Feller L, Wood NH, Khammissa RA et al (2010) Human papillomavirus-mediated carcinogenesis and HPV-associated oral and oropharyngealsquamous cell carcinoma. Part 1: human papillomavirus-mediated carcinogenesis. Head Face Med 6:14
Mirzayans R, Andrais B, Scott A et al (2012) New insights into p53 signaling and cancer cell response to DNA damage: implications for cancer therapy. J Biomed Biotechnol 2012:170325
Dai Y, Grant S (2010) New insights into checkpoint kinase 1 (Chk1) in the DNA damage response (DDR) signaling network: rationale for employing Chk1 inhibitors in cancer therapeutics. Clin Cancer Res 16:376–383
Machida YJ, Hamlin JL, Dutta A (2005) Right place, right time, and only once: replication initiation in metazoans. Cell 123:13–24
Boye E, Grallert B (2009) In DNA replication, the early bird catches the worm. Cell 136:812–814
Katsuno Y, Suzuki A, Sugimura K et al (2009) Cyclin A-Cdk1 regulates the origin firing program in mammalian cells. Proc Natl Acad Sci U S A 106:3184–3189
Soultanas P (2012) Loading mechanisms of ring helicases at replication origins. Mol Microbiol 84:6–16
Nethanel T, Reisfeld S, Dinter-Gottlieb G et al (1988) An Okazaki piece of simian virus 40 may be synthesized by ligation of shorter precursor chains. J Virol 62:2867–2873
Branzei D, Foiani M (2005) The DNA damage response during DNA replication. Curr Opin Cell Biol 17:568–575
Petermann E, Helleday T (2010) Pathways of mammalian replication fork restart. Nat Rev Mol Cell Biol 11:683–687
Branzei D, Foiani M (2009) The checkpoint response to replication stress. DNA Repair 8:1038–1046
Shimada K, Oma Y, Schleker T et al (2008) Ino80 chromatin remodeling complex promotes recovery of stalled replication forks. Curr Biol 18:566–575
Allen C, Ashley AK, Hromas R et al (2011) More forks on the road to replication stress recovery. J Mol Cell Biol 3:4–12
Saintigny Y, Delacote F, Vares G et al (2001) Characterization of homologous recombination induced by replication inhibition in mammalian cells. EMBO J 20:3861–3870
Uchida KS, Takagaki K, Kumada K et al (2009) Kinetochore stretching inactivates the spindle assembly checkpoint. J Cell Biol 184:383–390
May KM, Hardwick KG (2006) The spindle checkpoint. J Cell Sci 119:4139–4142
Cleveland DW, Mao Y, Sullivan KF (2003) Centromeres and kinetochores: from epigenetics to mitotic checkpoint signaling. Cell 112:407–421
Maiato H, DeLuca J, Salmon ED et al (2004) The dynamic kinetochore-microtubule interface. J Cell Sci 117:5461–5477
Musacchio A, Hardwick KG (2002) The spindle checkpoint: structural insights into dynamic signalling. Nat Rev Mol Cell Biol 3:731–741
Yu H (2002) Regulation of APC-Cdc20 by the spindle checkpoint. Curr Opin Cell Biol 14:706–714
Rieder CL, Cole RW, Khodjakov A et al (1995) The checkpoint delaying anaphase in response to chromosome monoorientation is mediated by an inhibitory signal produced by unattached kinetochores. J Cell Biol 130:941–948
Maresca TJ, Salmon ED (2009) Intrakinetochore stretch is associated with changes in kinetochore phosphorylation and spindle assembly checkpoint activity. J Cell Biol 184:373–381
Musacchio A (2011) Spindle assembly checkpoint: the third decade. Philos Trans R Soc Lond B Biol Sci 366:3595–3604
Skoufias DA, Andreassen PR, Lacroix FB et al (2001) Mammalian mad2 and bub1/bubR1 recognize distinct spindle attachment and kinetochore-tension checkpoints. Proc Natl Acad Sci U S A 98:4492–4497
Bharadwaj R, Yu H (2004) The spindle checkpoint, aneuploidy, and cancer. Oncogene 23:2016–2027
Smith ML, Seo YR (2002) p53 Regulation of DNA excision repair pathways. Mutagenesis 17:149–156
Lu X, Nguyen TA, Appella E et al (2004) Homeostatic regulation of base excision repair by a p53-induced phosphatase: linking stress response pathways with DNA repair proteins. Cell Cycle 3:1363–1366
Wilson DM 3rd, Kim D, Berquist BR et al (2011) Variation in base excision repair capacity. Mutat Res 711:100–112
Smith ML, Chen IT, Zhan Q et al (1995) Involvement of the p53 tumor suppressor in repair of UV-type DNA damage. Oncogene 10:1053–1059
Smith ML, Ford JM, Hollander MC et al (2000) p53-Mediated DNA repair responses to UV radiation: studies of mouse cells lacking p53, p21, and/or gadd45 genes. Mol Cell Biol 20:3705–3714
Li X, Coffino P (1996) High-risk human papilloma virus E6 protein has two distinct binding sites within p53, of which only one determines degradation. J Virol 70:4509–4516
McCubrey JA, Steelman LS, Chappell WH et al (2007) Roles of the Raf/Mek/Erk pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta 1773:1263–1284
Roos WP, Kaina B (2006) DNA damage-induced cell death by apoptosis. Trends Mol Med 12:440–450
Chen ZX, Riggs AD (2011) DNA methylation and demethylation in mammals. J Biol Chem 286:18347–18353
Downs JA (2007) Chromatin structure and DNA double-strand break responses in cancer progression and therapy. Oncogene 26:7765–7772
Baxevanis AD, Arents G, Moudrianakis EN et al (1995) A variety of DNA-binding and multimeric proteins contain the histone fold motif. Nucleic Acids Res 23:2685–2691
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer Science+Business Media New York
About this chapter
Cite this chapter
Yaegaki, K. (2014). The Role of p53 in Carcinogenesis and Apoptosis in Oral Tissues. In: Ekuni, D., Battino, M., Tomofuji, T., Putnins, E. (eds) Studies on Periodontal Disease. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4614-9557-4_7
Download citation
DOI: https://doi.org/10.1007/978-1-4614-9557-4_7
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4614-9556-7
Online ISBN: 978-1-4614-9557-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)