Characterization of a natural mutator variant of human DNA polymerase λ which promotes chromosomal instability by compromising NHEJ

PLoS ONE

Volumn 4, Issue 10, 2009, Pages

  Terrados, Gloria ^a   Capp, Jean Pascal ^b   Canitrot, Yvan ^c   García Díaz, Miguel ^a,d   Bebenek, Katarzyna ^d   Kirchhoff, Tomas ^a,e   Villanueva, Alberto ^f   Boudsocq, François ^c   Bergolio, Valélerie ^c   Cazaux, Christophe ^c   Kunkel, Thomas A ^d   Hoffmann, Jean Sébastien ^c   Blanco, Luis ^a  

^a CENTRO DE BIOLOGÍA MOLECULAR SEVERO OCHOA   (Spain)

^b CNRS   (France)

^c INSTITUT DE PHARMACOLOGIE ET DE BIOLOGIE STRUCTURALE   (France)

^d NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES   (United States)

^e MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^f CATALAN INSTITUTE OF ONCOLOGY   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

ARGININE; DEOXYRIBOSE PHOSPHATE LYASE; DNA POLYMERASE; DNA POLYMERASE LAMBDA; GENE PRODUCT; LYASE; TRYPTOPHAN; UNCLASSIFIED DRUG; AMINO ACID; DNA; DNA BINDING PROTEIN; DNA DIRECTED DNA POLYMERASE BETA; DNA POLYMERASE BETA2; NHEJ1 PROTEIN, HUMAN; POLYDEOXYRIBONUCLEOTIDE SYNTHASE;

AMINO ACID SUBSTITUTION; ARTICLE; CATALYSIS; CHROMOSOMAL INSTABILITY; CHROMOSOME ABERRATION; CODON; CONTROLLED STUDY; DNA REPAIR; DOUBLE STRANDED DNA BREAK; ENZYME ACTIVITY; GENE EXPRESSION; GENE FREQUENCY; GENE IDENTIFICATION; GENETIC VARIABILITY; HUMAN; HUMAN TISSUE; IN VITRO STUDY; MUTATIONAL ANALYSIS; NONHOMOLOGOUS END JOINING; PHENOTYPE; POLYMERIZATION; SINGLE NUCLEOTIDE POLYMORPHISM; CHEMISTRY; GENETICS; METABOLISM; MUTATION; NUCLEOTIDE SEQUENCE; PHYSIOLOGY;

MAMMALIA;

AMINO ACIDS; ARGININE; CHROMOSOMAL INSTABILITY; CHROMOSOME ABERRATIONS; CODON; DNA; DNA BREAKS, DOUBLE-STRANDED; DNA MUTATIONAL ANALYSIS; DNA POLYMERASE BETA; DNA REPAIR; DNA REPAIR ENZYMES; DNA-BINDING PROTEINS; HUMANS; MUTATION; POLYMORPHISM, SINGLE NUCLEOTIDE; TRYPTOPHAN;

EID: 70350221800     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0007290     Document Type: Article

References (49)

1. Hoeijmakers JH (2001) Genome maintenance mechanisms for preventing cancer. Nature 411: 366-374.
2. Hubscher U, Maga G, Spadari S (2002) Eukaryotic DNA polymerases. Annu Rev Biochem 71: 133-163.
3. Shcherbakova PV, Bebenek K, Kunkel TA (2003) Functions of eukaryotic DNA polymerases. Sci Aging Knowledge Environ 2003: RE3.
4. Garcia-Diaz M, Dominguez O, Lopez-Fernandez LA, de Lera LT, Saniger ML, et al. (2000) DNA polymerase lambda (Pol lambda), a novel eukaryotic DNA polymerase with a potential role in meiosis. J Mol Biol 301: 851-867.
5. Aoufouchi S, Flatter E, Dahan A, Faili A, Bertocci B, et al. (2000) Two novel human and mouse DNA polymerases of the polX family. Nucleic Acids Res 28: 3684-3693.
6. Nagasawa K, Kitamura K, Yasui A, Nimura Y, Ikeda K, et al. (2000) Identification and characterization of human DNA polymerase beta 2, a DNA polymerase beta -related enzyme. J Biol Chem 275: 31233-31238.
7. Garcia-Diaz M, Bebenek K, Krahn JM, Blanco L, Kunkel TA, et al. (2004) A structural solution for the DNA polymerase lambda-dependent repair of DNA gaps with minimal homology. Mol Cell 13: 561-572.
8. Garcia-Diaz M, Bebenek K, Sabariegos R, Dominguez O, Rodriguez J, et al. (2002) DNA polymerase lambda, a novel DNA repair enzyme in human cells. J Biol Chem 277: 13184-13191.
9. Garcia-Diaz M, Bebenek K, Kunkel TA, Blanco L (2001) Identification of an intrinsic 5′-deoxyribose-5-phosphate lyase activity in human DNA polymerase lambda: a possible role in base excision repair. J Biol Chem 276: 34659-34663.
10. Beard WA, Wilson SH (2000) Structural design of a eukaryotic DNA repair polymerase: DNA polymerase beta. Mutat Res 460: 231-244.
11. Sobol RW, Wilson SH (2001) Mammalian DNA beta-polymerase in base excision repair of alkylation damage. Prog Nucleic Acid Res Mol Biol 68: 57-74.
12. Braithwaite EK, Kedar PS, Lan L, Polosina YY, Asagoshi K, et al. (2005) DNA polymerase lambda protects mouse fibroblasts against oxidative DNA damage and is recruited to sites of DNA damage/repair. J Biol Chem 280: 31641-31647.
13. Braithwaite EK, Prasad R, Shock DD, Hou EW, Beard WA, et al. (2005) DNA polymerase lambda mediates a back-up base excision repair activity in extracts of mouse embryonic fibroblasts. J Biol Chem 280: 18469-18475.
14. Callebaut I, Mornon JP (1997) From BRCA1 to RAP1: a widespread BRCT module closely associated with DNA repair. FEBS Lett 400: 25-30.
15. Bork P, Hofmann K, Bucher P, Neuwald AF, Altschul SF, et al. (1997) A superfamily of conserved domains in DNA damage-responsive cell cycle checkpoint proteins. Faseb J 11: 68-76.
16. Fan W, Wu X (2004) DNA polymerase lambda can elongate on DNA substrates mimicking non-homologous end joining and interact with XRCC4-ligase IV complex. Biochem Biophys Res Commun 323: 1328-1333.
17. Ma Y, Lu H, Tippin B, Goodman MF, Shimazaki N, et al. (2004) A biochemically defined system for mammalian nonhomologous DNA end joining. Mol Cell 16: 701-713.
18. Nick McElhinny SA, Havener JM, Garcia-Diaz M, Juarez R, Bebenek K, et al. (2005) A gradient of template dependence defines distinct biological roles for family X polymerases in nonhomologous end joining. Mol Cell 19: 357-366.
19. Lee JW, Blanco L, Zhou T, Garcia-Diaz M, Bebenek K, et al. (2004) Implication of DNA polymerase lambda in alignment-based gap filling for nonhomologous DNA end joining in human nuclear extracts. J Biol Chem 279: 805-811.
20. Capp JP, Boudsocq F, Bertrand P, Laroche-Clary A, Pourquier P, et al. (2006) The DNA polymerase lambda is required for the repair of non-compatible DNA double strand breaks by NHEJ in mammalian cells. Nucleic Acids Res 34: 2998-3007.
21. Dobashi Y, Kubota Y, Shuin T, Torigoe S, Yao M, et al. (1995) Polymorphisms in the human DNA polymerase beta gene. Hum Genet 95: 389-390.
22. Bhattacharyya N, Banerjee S (1997) A variant of DNA polymerase beta acts as a dominant negative mutant. Proc Natl Acad Sci U S A 94: 10324-10329.
23. Lang T, Maitra M, Starcevic D, Li SX, Sweasy JB (2004) A DNA polymerase beta mutant from colon cancer cells induces mutations. Proc Natl Acad Sci U S A 101: 6074-6079.
24. Sweasy JB, Lang T, Starcevic D, Sun KW, Lai CC, et al. (2005) Expression of DNA polymerase {beta} cancer-associated variants in mouse cells results in cellular transformation. Proc Natl Acad Sci U S A 102: 14350-14355.
25. Kunkel T (2003) Considering the cancer consequences of altered DNA polymerase function. Cancer Cell 3: 105-110.
26. Ponamarev MV, Longley MJ, Nguyen D, Kunkel TA, Copeland WC (2002) Active site mutation in DNA polymerase gamma associated with progressive external ophthalmoplegia causes error-prone DNA synthesis. J Biol Chem 277: 15225-15228.
27. Osheroff WP, Jung HK, Beard WA, Wilson SH, Kunkel TA (1999a) The fidelity of DNA polymerase beta during distributive and processive DNA synthesis. J Biol Chem 274: 3642-3650.
28. Osheroff WP, Beard WA, Yin S, Wilson SH, Kunkel TA (2000) Minor groove interactions at the DNA polymerase beta active site modulate single-base deletion error rates. J Biol Chem 275: 28033-28038.
29. Kosa JL, Sweasy JB (1999) The E249K mutator mutant of DNA polymerase beta extends mispaired termini. J Biol Chem 274: 35866-35872.
30. Opresko PL, Sweasy JB, Eckert KA (1998) The mutator form of polymerase beta with amino acid substitution at tyrosine 265 in the hinge region displays an increase in both base substitution and frame shift errors. Biochemistry 37: 2111-2119.
31. Osheroff WP, Beard WA, Wilson SH, Kunkel TA (1999b) Base substitution specificity of DNA polymerase beta depends on interactions in the DNA minor groove. J Biol Chem 274: 20749-20752.
32. Dalal S, Hile S, Eckert KA, Sun KW, Starcevic D, et al. (2005) Prostate-cancer-associated I260M variant of DNA polymerase beta is a sequence-specific mutator. Biochemistry 44: 15664-15673.
33. Canitrot Y, Cazaux C, Frechet M, Bouayadi K, Lesca C, et al. (1998) Overexpression of DNA polymerase beta in cell results in a mutator phenotype and a decreased sensitivity to anticancer drugs. Proc Natl Acad Sci U S A 95: 12586-12590.
34. Garcia-Diaz M, Bebenek K, Krahn JM, Kunkel TA, Pedersen LC (2005) A closed conformation for the Pol lambda catalytic cycle. Nat Struct Mol Biol 12: 97-98.
35. Shah AM, Conn DA, Li SX, Capaldi A, Jager J, et al. (2001) A DNA polymerase beta mutator mutant with reduced nucleotide discrimination and increased protein stability. Biochemistry 40: 11372-11381.
36. Guirouilh-Barbat J, Huck S, Bertrand P, Pirzio L, Desmaze C, et al. (2004) Impact of the KU80 pathway on NHEJ-induced genome rearrangements in mammalian cells. Mol Cell 14: 611-623.
37. Karanjawala ZE, Grawunder U, Hsieh CL, Lieber MR (1999) The nonhomologous DNA end joining pathway is important for chromosome stability in primary fibroblasts. Curr Biol 9: 1501-1504.
38. Ferguson DO, Sekiguchi JM, Chang S, Frank KM, Gao Y, et al. (2000) The nonhomologous end-joining pathway of DNA repair is required for genomic stability and the suppression of translocations. Proc Natl Acad Sci U S A 97: 6630-6633.
39. Albertella MR, Lau A, O'Connor MJ (2005) The overexpression of specialized DNA polymerases in cancer. DNA Repair (Amst). 4(5): 583-93.
40. Gorgoulis VG, Vassiliou LV, Karakaidos P, Zacharatos P, Kotsinas A, et al. (2005) Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions. Nature 434: 907-913.
41. Miyamoto H, Miyagi Y, Ishikawa T, Ichikawa Y, Hosaka M, et al. (1999) DNA polymerase beta gene mutation in human breast cancer. Int J Cancer 83: 708-709.
42. Wang L, Patel U, Ghosh L, Banerjee S (1992) DNA polymerase beta mutations in human colorectal cancer. Cancer Res 52: 4824-4827.
43. Goldsby R, Lawrence N, Hays L, Olmsted E, Chen X, et al. (2001) Defective DNA polymerase-delta proofreading causes cancer susceptibility in mice. Nat Med 7: 638-639.
44. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100: 57-70.
45. Tomka M, Kirchhoff T, Kulcsar L, Stevurkova V, Zajac V (1998) The combination of heteroduplex analysis and protein truncation test for exact detection of the APC gene mutations. Neoplasma 45: 345-348.
46. Kirchhoff T, Kulcsar L, Tomka M, Stevurkova V, Zajac V (1999) Characterization of APC exon 15 germ-line mutation in FAP family with severe phenotype showing extracolonic symptoms. Neoplasma 46: 290-294.
47. Picher AJ, Blanco L (2007) Human DNA polymerase lambda is a proficient extender of primer ends paired to 7,8-dihydro-8-oxoguanine. DNA Repair (Amst) 6: 1749-1756.
48. Bebenek K, Kunkel TA (1995) Analyzing fidelity of DNA polymerases. Methods Enzymol 262: 217-232.
49. Bergoglio V, Pillaire MJ, Lacroix-Triki M, Raynaud-Messina B, Canitrot Y, et al. (2002) Deregulated DNA polymerase beta induces chromosome instability and tumorigenesis. Cancer Res 62: 3511-3514.