TP53 Regulates Transcription of DNA Repair Genes

Poletto M, Legrand AJ, Fletcher SC, Dianov GL. p53 coordinates base excision repair to prevent genomic instability. Nucleic Acids Res. 2016 Apr 20;44(7):3165–75. PMID: 26773055; PMCID: PMC4838360.; Ekumi KM, Paculova H, Lenasi T, Pospichalova V, Bösken CA, Rybarikova J, Bryja V, Geyer M, Blazek D, Barboric M. Ovarian carcinoma CDK12 mutations misregulate expression of DNA repair genes via deficient formation and function of the Cdk12/CycK complex. Nucleic Acids Res. 2015 Mar 11;43(5):2575–89. PMID: 25712099; PMCID: PMC4357706.; Bartkowiak B, Greenleaf AL. Expression, Purification, and Identification of Associated Proteins of the Full-length hCDK12/CyclinK Complex. Journal of Biological Chemistry. 2015 Jan;290(3):1786–95. doi: 10.1074/jbc.m114.612226.; Bösken CA, Farnung L, Hintermair C, Merzel Schachter M, Vogel-Bachmayr K, Blazek D, Anand K, Fisher RP, Eick D, Geyer M. The structure and substrate specificity of human Cdk12/Cyclin K. Nature Communications. 2014 Mar 24;5(1):3505. doi: 10.1038/ncomms4505.; Kuo M, Sy AJ, Xue L, Chi M, -C. Lee MT, Yen T, Chiang M, Chang L, Chu P, Yen Y. RRM2B Suppresses Activation of the Oxidative Stress Pathway and is Up-regulated by P53 During Senescence. Scientific Reports. 2012 Nov 08;2(1):822. doi: 10.1038/srep00822.; Cheng S-G, Kuzyk MA, Moradian A, Ichu T, Chang VC-, Tien JF, Vollett SE, Griffith M, Marra MA, Morin GB. Interaction of Cyclin-Dependent Kinase 12/CrkRS with Cyclin K1 Is Required for the Phosphorylation of the C-Terminal Domain of RNA Polymerase II. Molecular and Cellular Biology. 2012 Nov 01;32(22):4691–704. doi: 10.1128/mcb.06267-11.; Blazek D, Kohoutek J, Bartholomeeusen K, Johansen E, Hulinkova P, Luo Z, Cimermancic P, Ule J, Peterlin BM. The Cyclin K/Cdk12 complex maintains genomic stability via regulation of expression of DNA damage response genes. Genes Dev. 2011 Oct 15;25(20):2158–72. PMID: 22012619; PMCID: PMC3205586.; Cazzalini O, Scovassi AI, Savio M, Stivala LA, Prosperi E. Multiple roles of the cell cycle inhibitor p21CDKN1A in the DNA damage response. Mutation Research/Reviews in Mutation Research. 2010 Apr;704(1-3):12–20. doi: 10.1016/j.mrrev.2010.01.009.; Jegga AG, Inga A, Menendez D, Aronow BJ, Resnick MA. Functional evolution of the p53 regulatory network through its target response elements. Proc Natl Acad Sci U S A. 2008 Jan 22;105(3):944–9. PMID: 18187580; PMCID: PMC2242714.; Chen J, Sadowski I. Identification of the mismatch repair genes PMS2 and MLH1 as p53 target genes by using serial analysis of binding elements. Proc. Natl. Acad. Sci. U.S.A. 2005 Mar 21;102(13):4813–8. doi: 10.1073/pnas.0407069102.; Fitch ME, Cross IV, Ford JM. p53 responsive nucleotide excision repair gene products p48 and XPC, but not p53, localize to sites of UV-irradiation-induced DNA damage, in vivo. Carcinogenesis. 2003 May;24(5):843–50. doi: 10.1093/carcin/bgg031. PMID: 12771027.; Tan T, Chu G. p53 Binds and Activates the Xeroderma Pigmentosum DDB2 Gene in Humans but Not Mice. Molecular and Cellular Biology. 2002 May 01;22(10):3247–54. doi: 10.1128/mcb.22.10.3247-3254.2002.; Mori T, Anazawa Y, Matsui K, Fukuda S, Nakamura Y, Arakawa H. Cyclin K as a direct transcriptional target of the p53 tumor suppressor. Neoplasia. 2002 May;4(3):268–74. PMID: 11988847; PMCID: PMC1531701.; Amundson SA, Patterson A, Do KT, Fornace, Jr. AJ. A Nucleotide Excision Repair Master-Switch: p53 Regulated Coordinate Introduction of Global Genomic Repair Genes. Cancer Biology & Therapy. 2002 Mar 07;1(2):145–9. doi: 10.4161/cbt.59.; Warnick CT, Dabbas B, Ford CD, Strait KA. Identification of a p53 Response Element in the Promoter Region of the hMSH2 Gene Required for Expression in A2780 Ovarian Cancer Cells. Journal of Biological Chemistry. 2001 Jul;276(29):27363–70. doi: 10.1074/jbc.m103088200.; Scherer SJ, Maier SM, Seifert M, Hanselmann RG, Zang KD, Müller-Hermelink HK, Angel P, Welter C, Schartl M. p53 and c-Jun Functionally Synergize in the Regulation of the DNA Repair Gene hMSH2 in Response to UV. Journal of Biological Chemistry. 2000 Dec;275(48):37469–73. doi: 10.1074/jbc.m006990200.; Xu J, Morris GF. p53-Mediated Regulation of Proliferating Cell Nuclear Antigen Expression in Cells Exposed to Ionizing Radiation. Molecular and Cellular Biology. 1999 Jan 01;19(1):12–20. doi: 10.1128/mcb.19.1.12.; Liebetrau W, Budde A, Savoia A, Grummt F, Hoehn H. p53 activates Fanconi anemia group C gene expression. Hum Mol Genet. 1997 Feb;6(2):277–83. doi: 10.1093/hmg/6.2.277. PMID: 9063748.

Metabolites

ATP(4-)

Formula: C10H12N5O13P3 (502.9644492)

CAS ID:

ADP(3-)

Formula: C10H12N5O10P2 (424.0059412)

CAS ID:



Enzyme

EC Number name full name note
5.6.2.3 DNA 5'-3' helicase DNA 5'-3' helicase (ATP-hydrolysing)
5.6.2.4 DNA 3'-5' helicase DNA 3'-5' helicase (ATP-hydrolysing)


Proteins

Protein ID name full name