Mammalian ribonucleotide reductase subunit p53R2 is required for mitochondrial DNA replication and DNA repair in quiescent cells

Proceedings of the National Academy of Sciences of the United States of America

Volumn 109, Issue 33, 2012, Pages 13302-13307

  Pontarin, Giovanna ^a   Ferraro, Paola ^a   Bee, Leonardo ^a   Reichard, Peter ^a   Bianchi, Vera ^a  

^a UNIVERSITY OF PADOVA   (Italy)

Author keywords

Cell cycle; DNA precursors; dNTP de novo synthesis; Mitochondrial disease

Indexed keywords

DEOXYNUCLEOSIDE; DNA; DOUBLE STRANDED DNA; ETHIDIUM BROMIDE; HISTONE H2AX; MITOCHONDRIAL DNA; NUCLEOSIDE; RIBONUCLEOTIDE REDUCTASE; RIBONUCLEOTIDE REDUCTASE SUBUNIT P53R2; UNCLASSIFIED DRUG;

ARTICLE; CELL CYCLE REGULATION; CELL GROWTH; CELL MUTANT; CELL TRANSFORMATION; CONTROLLED STUDY; CULTURE MEDIUM; DNA DAMAGE; DNA REPAIR; DNA SYNTHESIS; FIBROBLAST; FLUOROMETRY; GENE MUTATION; HISTONE PHOSPHORYLATION; HUMAN; HUMAN CELL; MAMMAL; MITOCHONDRIAL DNA REPLICATION; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN DEPLETION; PROTEIN EXPRESSION; PROTEIN FUNCTION; ULTRAVIOLET IRRADIATION;

ANIMALS; CELL CYCLE PROTEINS; DNA REPAIR; DNA REPLICATION; DNA, MITOCHONDRIAL; ETHIDIUM; FIBROBLASTS; FLUORESCENCE; FLUOROMETRY; HISTONES; HUMANS; HYDROXYUREA; MAMMALS; MITOCHONDRIA; MUTATION; NUCLEIC ACID CONFORMATION; NUCLEOTIDES; PHOSPHORYLATION; PROTEIN SUBUNITS; RIBONUCLEOTIDE REDUCTASES; ULTRAVIOLET RAYS;

EID: 84865181704     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1211289109     Document Type: Article

References (38)

1. Nordlund P, Reichard P (2006) Ribonucleotide reductases. Annu Rev Biochem 75: 681-706. (Pubitemid 44118048)
2. Niida H, Shimada M, Murakami H, Nakanishi M (2010) Mechanisms of dNTP supply that play an essential role in maintaining genome integrity in eukaryotic cells. Cancer Sci 101:2505-2509.
3. Meuth M (1989) The molecular basis of mutations induced by deoxyribonucleoside triphosphate pool imbalances in mammalian cells. Exp Cell Res 181:305-316.
4. Kumar D, et al. (2011) Mechanisms of mutagenesis in vivo due to imbalanced dNTP pools. Nucleic Acids Res 39:1360-1371.
5. Chabes AL, Björklund S, Thelander L (2004) S phase-specific transcription of the mouse ribonucleotide reductase R2 gene requires both a proximal repressive E2F-binding site and an upstream promoter activating region. J Biol Chem 279:10796-10807. (Pubitemid 38372692)
6. Håkansson P, Hofer A, Thelander L (2006) Regulation of mammalian ribonucleotide reduction and dNTP pools after DNA damage and in resting cells. J Biol Chem 281: 7834-7841. (Pubitemid 43847398)
7. Pontarin G, et al. (2007) p53R2-dependent ribonucleotide reduction provides deoxyribonucleotides in quiescent human fibroblasts in the absence of induced DNA damage. J Biol Chem 282:16820-16828. (Pubitemid 47093192)
8. Chabes AL, Pfleger CM, Kirschner MW, Thelander L (2003) Mouse ribonucleotide reductase R2 protein: A new target for anaphase-promoting complex Cdh1-mediated proteolysis. Proc Natl Acad Sci USA 100:3925-3929. (Pubitemid 36418133)
9. Tanaka H, et al. (2000) A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage. Nature 404:42-49. (Pubitemid 30143125)
10. Pontarin G, et al. (2008) Ribonucleotide reduction is a cytosolic process in mammalian cells independently of DNA damage. Proc Natl Acad Sci USA 105:17801-17806.
11. Bourdon A, et al. (2007) Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion. Nat Genet 39: 776-780. (Pubitemid 46848590)
12. Bornstein B, et al. (2008) Mitochondrial DNA depletion syndrome due to mutations in the RRM2B gene. Neuromuscul Disord 18:453-459.
13. Acham-Roschitz B, et al. (2009) A novel mutation of the RRM2B gene in an infant with early fatal encephalomyopathy, central hypomyelination, and tubulopathy. Mol Genet Metab 98:300-304.
14. Tyynismaa H, et al. (2009) A heterozygous truncating mutation in RRM2B causes autosomal-dominant progressive external ophthalmoplegia with multiple mtDNA deletions. Am J Hum Genet 85:290-295.
15. Shaibani A, et al. (2009) Mitochondrial neurogastrointestinal encephalopathy due to mutations in RRM2B. Arch Neurol 66:1028-1032.
16. Kollberg G, et al. (2009) A novel homozygous RRM2B missense mutation in association with severe mtDNA depletion. Neuromuscul Disord 19:147-150.
17. Devlin HL, et al. (2008) Impairment of the DNA repair and growth arrest pathways by p53R2 silencing enhances DNA damage-induced apoptosis in a p53-dependent manner in prostate cancer cells. Mol Cancer Res 6:808-818.
18. Kunos CA, et al. (2010) Ribonucleotide reductase inhibition enhances chemoradiosensitivity of human cervical cancers. Radiat Res 174:574-581.
19. Nakano K, Bálint E, Ashcroft M, Vousden KH (2000) A ribonucleotide reductase gene is a transcriptional target of p53 and p73. Oncogene 19:4283-4289.
20. Pontarin G, et al. (2011) Deoxyribonucleotide metabolism in cycling and resting human fibroblasts with a missense mutation in p53R2, a subunit of ribonucleotide reductase. J Biol Chem 286:11132-11140.
21. King MP, Attardi G (1996) Isolation of human cell lines lacking mitochondrial DNA. Methods Enzymol 264:304-313. (Pubitemid 26089319)
22. Arnér ES, Eriksson S (1995) Mammalian deoxyribonucleoside kinases. Pharmacol Ther 67:155-186.
23. Krakoff IH, Brown NC, Reichard P (1968) Inhibition of ribonucleoside diphosphate reductase by hydroxyurea. Cancer Res 28:1559-1565.
24. Friedberg E, et al. (2006) DNA Repair and Mutagenesis (ASM Press, Washington, DC).
25. Erixon K, Ahnström G (1979) Single-strand breaks in DNA during repair of UV-induced damage in normal human and xeroderma pigmentosum cells as determined by alkaline DNA unwinding and hydroxylapatite chromatography: Effects of hydroxyurea, 5-fluorodeoxyuridine and 1-beta-D-arabinofuranosylcytosine on the kinetics of repair. Mutat Res 59:257-271. (Pubitemid 9093437)
26. Baumstark-Khan C, Hentschel U, Nikandrova Y, Krug J, Horneck G (2000) Fluorometric analysis of DNA unwinding (FADU) as a method for detecting repair-induced DNA strand breaks in UV-irradiated mammalian cells. Photochem Photobiol 72:477-484.
27. Birnboim HC, Jevcak JJ (1981) Fluorometric method for rapid detection of DNA strand breaks in human white blood cells produced by low doses of radiation. Cancer Res 41: 1889-1892. (Pubitemid 11114591)
28. Huberman JA (1981) New views of the biochemistry of eucaryotic DNA replication revealed by aphidicolin, an unusual inhibitor of DNA polymerase alpha. Cell 23: 647-648.
29. Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM (1998) DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem 273: 5858-5868. (Pubitemid 28124064)
30. Paull TT, et al. (2000) A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage. Curr Biol 10:886-895. (Pubitemid 30647617)
31. Marti TM, Hefner E, Feeney L, Natale V, Cleaver JE (2006) H2AX phosphorylation within the G1 phase after UV irradiation depends on nucleotide excision repair and not DNA double-strand breaks. Proc Natl Acad Sci USA 103:9891-9896. (Pubitemid 43993593)
32. Matsumoto M, et al. (2007) Perturbed gap-filling synthesis in nucleotide excision repair causes histone H2AX phosphorylation in human quiescent cells. J Cell Sci 120: 1104-1112. (Pubitemid 46638523)
33. Cleaver JE (2011) ?H2Ax: Biomarker of damage or functional participant in DNA repair "all that glitters is not gold!". Photochem Photobiol 87:1230-1239.
34. Rampazzo C, et al. (2010) Regulation by degradation, a cellular defense against deoxyribonucleotide pool imbalances. Mutat Res 703:2-10.
35. Spinazzola A, et al. (2009) Clinical and molecular features of mitochondrial DNA depletion syndromes. J Inherit Metab Dis 32:143-158.
36. Chaouch S, et al. (2009) Immortalized skin fibroblasts expressing conditional MyoD as a renewable and reliable source of converted human muscle cells to assess therapeutic strategies for muscular dystrophies: Validation of an exon-skipping approach to restore dystrophin in Duchenne muscular dystrophy cells. Hum Gene Ther 20: 784-790.
37. Schramm VL (2002) Development of transition state analogues of purine nucleoside phosphorylase as anti-T-cell agents. Biochim Biophys Acta 1587:107-117.
38. Carson DA, Seegmiller JE (1976) Effect of adenosine deaminase inhibition upon human lymphocyte blastogenesis. J Clin Invest 57:274-282.