ATM–Dependent MiR-335 Targets CtIP and Modulates the DNA Damage Response
ATM plays a critical role in cellular responses to DNA double-strand breaks (DSBs). We describe a new ATM–mediated DSB–induced DNA damage response pathway involving microRNA (miRNA): irradiation (IR)-induced DSBs activate ATM, which leads to the downregulation of miR-335, a miRNA that targets CtIP, which is an important trigger of DNA end resection in homologous recombination repair (HRR). We demonstrate that CREB is responsible for a large portion of miR-335 expression by binding to the promoter region of miR-335. CREB binding is greatly reduced after IR, corroborating with previous studies that IR-activated ATM phosphorylates CREB to reduce its transcription activity. Overexpression of miR-335 in HeLa cells resulted in reduced CtIP levels and post-IR colony survival and BRCA1 foci formation. Further, in two patient-derived lymphoblastoid cell lines with decreased post-IR colony survival, a “radiosensitive” phenotype, we demonstrated elevated miR-335 expression, reduced CtIP levels, and reduced BRCA1 foci formation. Colony survival, BRCA1 foci, and CtIP levels were partially rescued by miRNA antisense AMO-miR-335 treatment. Taken together, these findings strongly suggest that an ATM–dependent CREB–miR-335–CtIP axis influences the selection of HRR for repair of certain DSB lesions.
Vyšlo v časopise:
ATM–Dependent MiR-335 Targets CtIP and Modulates the DNA Damage Response. PLoS Genet 9(5): e32767. doi:10.1371/journal.pgen.1003505
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1003505
Souhrn
ATM plays a critical role in cellular responses to DNA double-strand breaks (DSBs). We describe a new ATM–mediated DSB–induced DNA damage response pathway involving microRNA (miRNA): irradiation (IR)-induced DSBs activate ATM, which leads to the downregulation of miR-335, a miRNA that targets CtIP, which is an important trigger of DNA end resection in homologous recombination repair (HRR). We demonstrate that CREB is responsible for a large portion of miR-335 expression by binding to the promoter region of miR-335. CREB binding is greatly reduced after IR, corroborating with previous studies that IR-activated ATM phosphorylates CREB to reduce its transcription activity. Overexpression of miR-335 in HeLa cells resulted in reduced CtIP levels and post-IR colony survival and BRCA1 foci formation. Further, in two patient-derived lymphoblastoid cell lines with decreased post-IR colony survival, a “radiosensitive” phenotype, we demonstrated elevated miR-335 expression, reduced CtIP levels, and reduced BRCA1 foci formation. Colony survival, BRCA1 foci, and CtIP levels were partially rescued by miRNA antisense AMO-miR-335 treatment. Taken together, these findings strongly suggest that an ATM–dependent CREB–miR-335–CtIP axis influences the selection of HRR for repair of certain DSB lesions.
Zdroje
1. HarperJW, ElledgeSJ (2007) The DNA damage response: ten years after. Mol Cell 28: 739–745.
2. BartekJ, BartkovaJ, LukasJ (2007) DNA damage signalling guards against activated oncogenes and tumour progression. Oncogene 26: 7773–7779.
3. JacksonSP, BartekJ (2009) The DNA-damage response in human biology and disease. Nature 461: 1071–1078.
4. HuenMS, ChenJ (2010) Assembly of checkpoint and repair machineries at DNA damage sites. Trends Biochem Sci 35: 101–108.
5. BartelDP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136: 215–233.
6. HuH, GattiRA (2011) MicroRNAs: new players in the DNA damage response. J Mol Cell Biol 3: 151–158.
7. LavinMF (2008) Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer. Nat Rev Mol Cell Biol 9: 759–769.
8. ShilohY (2006) The ATM-mediated DNA-damage response: taking shape. Trends Biochem Sci 31: 402–410.
9. MatsuokaS, BallifBA, SmogorzewskaA, McDonaldER3rd, HurovKE, et al. (2007) ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science 316: 1160–1166.
10. RoyK, WangL, MakrigiorgosGM, PriceBD (2006) Methylation of the ATM promoter in glioma cells alters ionizing radiation sensitivity. Biochem Biophys Res Commun 344: 821–826.
11. KimWJ, VoQN, ShrivastavM, LataxesTA, BrownKD (2002) Aberrant methylation of the ATM promoter correlates with increased radiosensitivity in a human colorectal tumor cell line. Oncogene 21: 3864–3871.
12. BerkovichE, GinsbergD (2003) ATM is a target for positive regulation by E2F-1. Oncogene 22: 161–167.
13. HuH, DuL, NagabayashiG, SeegerRC, GattiRA (2010) ATM is down-regulated by N-Myc-regulated microRNA-421. Proc Natl Acad Sci U S A 107: 1506–1511.
14. WangY, YuY, TsuyadaA, RenX, WuX, et al. (2011) Transforming growth factor-beta regulates the sphere-initiating stem cell-like feature in breast cancer through miRNA-181 and ATM. Oncogene 30: 1470–1480.
15. YanD, NgWL, ZhangX, WangP, ZhangZ, et al. (2010) Targeting DNA-PKcs and ATM with miR-101 sensitizes tumors to radiation. PLoS ONE 5: e11397 doi:10.1371/journal.pone.0011397.
16. RogersPB, PlowmanPN, HarrisSJ, ArlettCF (2000) Four radiation hypersensitivity cases and their implications for clinical radiotherapy. Radiotherapy and Oncology 57: 143–154.
17. MansourWY, BogdanovaNV, Kasten-PisulaU, RieckmannT, KocherS, et al. (2013) Aberrant overexpression of miR-421 downregulates ATM and leads to a pronounced DSB repair defect and clinical hypersensitivity in SKX squamous cell carcinoma. Radiotherapy and oncology 106: 147–54.
18. ZhangX, WanG, BergerFG, HeX, LuX (2011) The ATM kinase induces microRNA biogenesis in the DNA damage response. Mol Cell 41: 371–383.
19. KawaiS, AmanoA (2012) BRCA1 regulates microRNA biogenesis via the DROSHA microprocessor complex. The Journal of Cell Biology 197: 201–208.
20. ChenL, NieveraCJ, LeeAY-L, WuX (2008) Cell Cycle-dependent Complex Formation of BRCA1/CtIP/MRN Is Important for DNA Double-strand Break Repair. Journal of Biological Chemistry 283: 7713–7720.
21. HuenMSY, SySMH, ChenJ (2010) BRCA1 and its toolbox for the maintenance of genome integrity. Nat Rev Mol Cell Biol 11: 138–148.
22. XuB, KimS-t, KastanMB (2001) Involvement of Brca1 in S-Phase and G2-Phase Checkpoints after Ionizing Irradiation. Mol Cell Biol 21: 3445–3450.
23. SunX, Becker-CataniaSG, ChunHH, HwangMJ, HuoY, et al. (2002) Early diagnosis of ataxia-telangiectasia using radiosensitivity testing. The Journal of Pediatrics 140: 724–731.
24. PollardJM, GattiRA (2009) Clinical Radiation Sensitivity With DNA Repair Disorders: An Overview. International Journal of Radiation Oncology*Biology*Physics 74: 1323–1331.
25. NahasSA, DaviesR, FikeF, NakamuraK, DuL, et al. (2012) Comprehensive Profiling of Radiosensitive Human Cell Lines with DNA Damage Response Assays Identifies the Neutral Comet Assay as a Potential Surrogate for Clonogenic Survival. Radiation Research 177: 176–186.
26. DaviesRC, PettijohnK, FikeF, WangJ, NahasSA, et al. (2012) Defective DNA double-strand break repair in pediatric systemic lupus erythematosus. Arthritis Rheum 64: 568–578.
27. DevganSS, SanalO, DoilC, NakamuraK, NahasSA, et al. (2011) Homozygous deficiency of ubiquitin-ligase ring-finger protein RNF168 mimics the radiosensitivity syndrome of ataxia-telangiectasia. Cell Death Differ 18: 1500–1506.
28. MartinNT, NahasSA, TunuguntlaR, FikeF, GattiRA (2011) Assessing ‘radiosensitivity’ with kinetic profiles of gamma-H2AX, 53BP1 and BRCA1 foci. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 101: 35–38.
29. TavazoieSF, AlarconC, OskarssonT, PaduaD, WangQ, et al. (2008) Endogenous human microRNAs that suppress breast cancer metastasis. Nature 451: 147–152.
30. PngKJ, YoshidaM, ZhangXH, ShuW, LeeH, et al. (2011) MicroRNA-335 inhibits tumor reinitiation and is silenced through genetic and epigenetic mechanisms in human breast cancer. Genes Dev 25: 226–231.
31. NishitaY, YoshidaI, SadoT, TakagiN (1996) Genomic imprinting and chromosomal localization of the human MEST gene. Genomics 36: 539–542.
32. TakedaS, NakamuraK, TaniguchiY, PaullTT (2007) Ctp1/CtIP and the MRN complex collaborate in the initial steps of homologous recombination. Mol Cell 28: 351–352.
33. SmirnovDA, CheungVG (2008) ATM gene mutations result in both recessive and dominant expression phenotypes of genes and microRNAs. Am J Hum Genet 83: 243–253.
34. HicksonI, ZhaoY, RichardsonCJ, GreenSJ, MartinNMB, et al. (2004) Identification and Characterization of a Novel and Specific Inhibitor of the Ataxia-Telangiectasia Mutated Kinase ATM. Cancer Research 64: 9152–9159.
35. RonchettiD, LionettiM, MoscaL, AgnelliL, AndronacheA, et al. (2008) An integrative genomic approach reveals coordinated expression of intronic miR-335, miR-342, and miR-561 with deregulated host genes in multiple myeloma. BMC Med Genomics 1: 37.
36. ShiY, VenkataramanSL, DodsonGE, MabbAM, LeBlancS, et al. (2004) Direct regulation of CREB transcriptional activity by ATM in response to genotoxic stress. Proc Natl Acad Sci U S A 101: 5898–5903.
37. YunMH, HiomK (2009) CtIP-BRCA1 modulates the choice of DNA double-strand-break repair pathway throughout the cell cycle. Nature 459: 460–463.
38. YouZ, BailisJM (2010) DNA damage and decisions: CtIP coordinates DNA repair and cell cycle checkpoints. Trends Cell Biol 20: 402–409.
39. HouldsworthJ, LavinMF (1980) Effect of ionizing radiation on DNA synthesis in ataxia telangiectasia cells. Nucleic Acids Res 8: 3709–3720.
40. PainterRB, YoungBR (1980) Radiosensitivity in ataxia-telangiectasia: a new explanation. Proceedings of the National Academy of Sciences of the United States of America 77: 7315–7317.
41. YuX, ChenJ (2004) DNA damage-induced cell cycle checkpoint control requires CtIP, a phosphorylation-dependent binding partner of BRCA1 C-terminal domains. Mol Cell Biol 24: 9478–9486.
42. CousineauI, AbajiC, BelmaazaA (2005) BRCA1 regulates RAD51 function in response to DNA damage and suppresses spontaneous sister chromatid replication slippage: Implications for sister chromatid cohesion, genome stability, and carcinogenesis. Cancer Research 65: 11384–11391.
43. JohnsonN, CaiD, KennedyRD, PathaniaS, AroraM, et al. (2009) Cdk1 participates in BRCA1-dependent S phase checkpoint control in response to DNA damage. Molecular Cell 35: 327–339.
44. QvistP, HuertasP, JimenoS, NyegaardM, HassanMJ, et al. (2011) CtIP Mutations Cause Seckel and Jawad Syndromes. PLoS Genet 7: e1002310 doi:10.1371/journal.pgen.1002310.
45. LaiCH, ChunHH, NahasSA, MituiM, GamoKM, et al. (2004) Correction of ATM gene function by aminoglycoside-induced read-through of premature termination codons. Proc Natl Acad Sci U S A 101: 15676–15681.
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2013 Číslo 5
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
Najčítanejšie v tomto čísle
- Using Extended Genealogy to Estimate Components of Heritability for 23 Quantitative and Dichotomous Traits
- HDAC7 Is a Repressor of Myeloid Genes Whose Downregulation Is Required for Transdifferentiation of Pre-B Cells into Macrophages
- Female Bias in and Regulation by the Histone Demethylase KDM6A
- High-Resolution Transcriptome Maps Reveal Strain-Specific Regulatory Features of Multiple Isolates