A synthetic lethal siRNA screen identifying genes mediating sensitivity to a PARP inhibitor

EMBO Journal

Volumn 27, Issue 9, 2008, Pages 1368-1377

  Turner, Nicholas C ^a   Lord, Christopher J ^a   Iorns, Elizabeth ^a   Brough, Rachel ^a   Swift, Sally ^a   Elliott, Richard ^a   Rayter, Sydonia ^a   Tutt, Andrew N ^b   Ashworth, Alan ^a  

^a INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^b GUY S HOSPITAL   (United Kingdom)

Author keywords

CDK5; Cell cycle; DNA repair; Poly(ADP)ribose polymerase; RNAi screen

Indexed keywords

BRCA1 PROTEIN; BRCA2 PROTEIN; CYCLIN DEPENDENT KINASE 5; MITOGEN ACTIVATED PROTEIN KINASE 12; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE INHIBITOR; POLO LIKE KINASE 3; SMALL INTERFERING RNA;

ARTICLE; CELL CYCLE G2 PHASE; CELL CYCLE M PHASE; CONTROLLED STUDY; DNA DAMAGE; ENZYME INHIBITION; GENE SILENCING; HUMAN; HUMAN CELL; PRIORITY JOURNAL;

BLOTTING, WESTERN; CELL CYCLE; CELL LINE, TUMOR; CYCLIN-DEPENDENT KINASE 5; DNA DAMAGE; DNA REPAIR; FLOW CYTOMETRY; FLUORESCENT ANTIBODY TECHNIQUE; HELA CELLS; HUMANS; HYDROGEN PEROXIDE; MITOGEN-ACTIVATED PROTEIN KINASE 12; POLY(ADP-RIBOSE) POLYMERASES; PROTEIN-SERINE-THREONINE KINASES; RNA, SMALL INTERFERING; TRANSFECTION;

EID: 43249085571     PISSN: 02614189     EISSN: 14602075     Source Type: Journal    
DOI: 10.1038/emboj.2008.61     Document Type: Article

References (41)

1. Aza-Blanc P, Cooper CL, Wagner K, Batalov S, Deveraux QL, Cooke MP (2003) Identification of modulators of TRAIL-induced apoptosis via RNAi-based phenotypic screening. Mol Cell 12: 627-637
2. Bahassi el M, Hennigan RF, Myer DL, Stambrook PJ (2004) Cdc25C phosphorylation on serine 191 by Plk3 promotes its nuclear translocation. Oncogene 23: 2658-2663
3. Bai C, Sen P, Hofmann K, Ma L, Goebl M, Harper JW, Elledge SJ (1996) SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box. Cell 86: 263-274
4. Bartek J, Lukas C, Lukas J (2004) Checking on DNA damage in S phase. Nat Rev Mol Cell Biol 5: 792-804
5. Bartz SR, Zhang Z, Burchard J, Imakura M, Martin M, Palmieri A, Needham R, Guo J, Gordon M, Chung N, Warrener P, Jackson AL, Carleton M, Oatley M, Locco L, Santini F, Smith T, Kunapuli P, Ferrer M, Strulovici B et al (2006) Small interfering RNA screens reveal enhanced cisplatin cytotoxicity in tumor cells having both BRCA network and TP53 disruptions. Mol Cell Biol 26: 9377-9386
6. Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, Kyle S, Meuth M, Curtin NJ, Helleday T (2005) Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 434: 913-917
7. Chappell C, Hanakahi LA, Karimi-Busheri F, Weinfeld M, West SC (2002) Involvement of human polynucleotide kinase in doublestrand break repair by non-homologous end joining. EMBO J 21: 2827-2832
8. Chen X, Cheung ST, So S, Fan ST, Barry C, Higgins J, Lai KM, Ji J, Dudoit S, Ng IO, Van De Rijn M, Botstein D, Brown PO (2002) Gene expression patterns in human liver cancers. Mol Biol Cell 13: 1929-1939
9. Chin K, DeVries S, Fridlyand J, Spellman PT, Roydasgupta R, Kuo WL, Lapuk A, Neve RM, Qian Z, Ryder T, Chen F, Feiler H, Tokuyasu T, Kingsley C, Dairkee S, Meng Z, Chew K, Pinkel D, Jain A, Ljung BM et al (2006) Genomic and transcriptional aberrations linked to breast cancer pathophysiologies. Cancer Cell 10: 529-541
10. Ciullo M, Debily MA, Rozier L, Autiero M, Billault A, Mayau V, El Marhomy S, Guardiola J, Bernheim A, Coullin P, Piatier-Tonneau D, Debatisse M (2002) Initiation of the breakage-fusion-bridge mechanism through common fragile site activation in human breast cancer cells: the model of PIP gene duplication from a break at FRA7I. Hum Mol Genet 11: 2887-2894
11. Cruz JC, Tsai LH (2004) Cdk5 deregulation in the pathogenesis of Alzheimer's disease. Trends Mol Med 10: 452-458
12. Dhavan R, Tsai LH (2001) A decade of CDK5. Nat Rev Mol Cell Biol 2: 749-759
13. Echeverri CJ, Beachy PA, Baum B, Boutros M, Buchholz F, Chanda SK, Downward J, Ellenberg J, Fraser AG, Hacohen N, Hahn WC, Jackson AL, Kiger A, Linsley PS, Lum L, Ma Y, Mathey-Prevot B, Root DE, Sabatini DM, Taipale J et al (2006) Minimizing the risk of reporting false positives in large-scale RNAi screens. Nat Methods 3: 777-779
14. Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, Santarosa M, Dillon KJ, Hickson I, Knights C, Martin NM, Jackson SP, Smith GC, Ashworth A (2005) Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434: 917-921
15. Goldberg M, Stucki M, Falck J, D'Amours D, Rahman D, Pappin D, Bartek J, Jackson SP (2003) MDC1 is required for the intra-Sphase DNA damage checkpoint. Nature 421: 952-956
16. Graudens E, Boulanger V, Mollard C, Mariage-Samson R, Barlet X, Gremy G, Couillault C, Lajemi M, Piatier-Tonneau D, Zaborski P, Eveno E, Auffray C, Imbeaud S (2006) Deciphering cellular states of innate tumor drug responses. Genome Biol 7: R19
17. Hickson I, Zhao Y, Richardson CJ, Green SJ, Martin NM, Orr AI, Reaper PM, Jackson SP, Curtin NJ, Smith GC (2004) Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM. Cancer Res 64: 9152-9159
18. Hoeijmakers JH (2001) Genome maintenance mechanisms for preventing cancer. Nature 411: 366-374
19. Iorns E, Lord CJ, Turner N, Ashworth A (2007) Utilizing RNA interference to enhance cancer drug discovery. Nat Rev Drug Discov 6: 556-568
20. Jazayeri A, Falck J, Lukas C, Bartek J, Smith GC, Lukas J, Jackson SP (2006) ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks. Nat Cell Biol 8: 37-45
21. Jilani A, Ramotar D, Slack C, Ong C, Yang XM, Scherer SW, Lasko DD (1999) Molecular cloning of the human gene, PNKP, encoding a polynucleotide kinase 30-phosphatase and evidence for its role in repair of DNA strand breaks caused by oxidative damage. J Biol Chem 274: 24176-24186
22. Lee JH, Kim KT (2007) Regulation of cyclin-dependent kinase 5 and p53 by ERK1/2 pathway in the DNA damage-induced neuronal death. J Cell Physiol 210: 784-797
23. Mailand N, Podtelejnikov AV, Groth A, Mann M, Bartek J, Lukas J (2002) Regulation of G(2)/M events by Cdc25A through phosphorylation-dependent modulation of its stability. EMBO J 21: 5911-5920
24. McCabe N, Turner NC, Lord CJ, Kluzek K, Bialkowska A, Swift S, Giavara S, O'Connor MJ, Tutt AN, Zdzienicka MZ, Smith GC, Ashworth A (2006) Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition. Cancer Res 66: 8109-8115
25. Meister G, Tuschl T (2004) Mechanisms of gene silencing by doublestranded RNA. Nature 431: 343-349
26. Moynahan ME, Chiu JW, Koller BH, Jasin M (1999) Brca1 controls homology-directed DNA repair. Mol Cell 4: 511-518
27. Mukherji M, Bell R, Supekova L, Wang Y, Orth AP, Batalov S, Miraglia L, Huesken D, Lange J, Martin C, Sahasrabudhe S, Reinhardt M, Natt F, Hall J, Mickanin C, Labow M, Chanda SK, Cho CY, Schultz PG (2006) Genome-wide functional analysis of human cell-cycle regulators. Proc Natl Acad Sci USA 103: 14819-14824
28. Patrick GN, Zukerberg L, Nikolic M, de la Monte S, Dikkes P, Tsai LH (1999) Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration. Nature 402: 615-622
29. Pierce AJ, Johnson RD, Thompson LH, Jasin M (1999) XRCC3 promotes homology-directed repair of DNA damage in mammalian cells. Genes Dev 13: 2633-2638
30. Renwick A, Thompson D, Seal S, Kelly P, Chagtai T, Ahmed M, North B, Jayatilake H, Barfoot R, Spanova K, McGuffog L, Evans DG, Eccles D, Easton DF, Stratton MR, Rahman N (2006) ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles. Nat Genet 38: 873-875
31. Sanchez-Carbayo M, Socci ND, Lozano J, Saint F, Cordon-Cardo C (2006) Defining molecular profiles of poor outcome in patients with invasive bladder cancer using oligonucleotide microarrays. J Clin Oncol 24: 778-789
32. Strocchi P, Pession A, Dozza B (2003) Upregulation of cDK5/p35 by oxidative stress in human neuroblastoma IMR-32 cells. J Cell Biochem 88: 758-765
33. Tutt A, Bertwistle D, Valentine J, Gabriel A, Swift S, Ross G, Griffin C, Thacker J, Ashworth A (2001) Mutation in Brca2 stimulates error-prone homology-directed repair of DNA double-strand breaks occurring between repeated sequences. EMBO J 20: 4704-4716
34. van den Heuvel S, Harlow E (1993) Distinct roles for cyclin-dependent kinases in cell cycle control. Science 262: 2050-2054
35. Wang X, McGowan CH, Zhao M, He L, Downey JS, Fearns C, Wang Y, Huang S, Han J (2000) Involvement of the MKK6-p38gamma cascade in gamma-radiation-induced cell cycle arrest. Mol Cell Biol 20: 4543-4552
36. Wong KK, Chang S, Weiler SR, Ganesan S, Chaudhuri J, Zhu C, Artandi SE, Rudolph KL, Gottlieb GJ, Chin L, Alt FW, DePinho RA (2000) Telomere dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation. Nat Genet 26: 85-88
37. Woods J, Snape M, Smith MA (2007) The cell cycle hypothesis of Alzheimer's disease: suggestions for drug development. Biochim Biophys Acta 1772: 503-508
38. Yap TA, Boss DS, Fong PC, Roelvink M, Tutt A, Carmichael J, O'Connor MJ, Kaye SB, Schellens JH, de Bono J (2007) First in human phase I pharmacokinetic (PK) and pharmacodynamic (PD) study of KU-0059436 (Ku), a small molecule inhibitor of poly ADP-ribose polymerase (PARP) in cancer patients (p), including BRCA1/2 mutation carriers. J Clin Oncol 25: A3529
39. Zhang JH, Chung TD, Oldenburg KR (1999) A simple statistical parameter for use in evaluation and validation of high throughput screening assays. J Biomol Screen 4: 67-73
40. Zhu XH, Nguyen H, Halicka HD, Traganos F, Koff A (2004) Noncatalytic requirement for cyclin A-cdk2 in p27 turnover. Mol Cell Biol 24: 6058-6066
41. Zimmerman WC, Erikson RL (2007) Polo-like kinase 3 is required for entry into S phase. Proc Natl Acad Sci USA 104: 1847-1852