Cancer-associated mutations in the iron-sulfur domain of FANCJ affect G-quadruplex metabolism
Autoři:
Diana C. Odermatt aff001; Wei Ting C. Lee aff002; Sebastian Wild aff001; Stanislaw K. Jozwiakowski aff001; Eli Rothenberg aff002; Kerstin Gari aff001
Působiště autorů:
Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland
aff001; Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, United States of America
aff002
Vyšlo v časopise:
Cancer-associated mutations in the iron-sulfur domain of FANCJ affect G-quadruplex metabolism. PLoS Genet 16(6): e32767. doi:10.1371/journal.pgen.1008740
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1008740
Souhrn
FANCJ/BRIP1 is an iron-sulfur (FeS) cluster-binding DNA helicase involved in DNA inter-strand cross-link (ICL) repair and G-quadruplex (G4) metabolism. Mutations in FANCJ are associated with Fanconi anemia and an increased risk for developing breast and ovarian cancer. Several cancer-associated mutations are located in the FeS domain of FANCJ, but how they affect FeS cluster binding and/or FANCJ activity has remained mostly unclear. Here we show that the FeS cluster is indispensable for FANCJ’s ability to unwind DNA substrates in vitro and to provide cellular resistance to agents that induce ICLs. Moreover, we find that FANCJ requires an intact FeS cluster for its ability to unfold G4 structures on the DNA template in a primer extension assay with the lagging-strand DNA polymerase delta. Surprisingly, however, FANCJ variants that are unable to bind an FeS cluster and to unwind DNA in vitro can partially suppress the formation of replisome-associated G4 structures that we observe in a FANCJ knock-out cell line. This may suggest a partially retained cellular activity of FANCJ variants with alterations in the FeS domain. On the other hand, FANCJ knock-out cells expressing FeS cluster-deficient variants display a similar–enhanced–sensitivity towards pyridostatin (PDS) and CX-5461, two agents that stabilise G4 structures, as FANCJ knock-out cells. Mutations in FANCJ that abolish FeS cluster binding may hence be predictive of an increased cellular sensitivity towards G4-stabilising agents.
Klíčová slova:
ATP hydrolysis – Cysteine – DNA replication – DNA structure – DNA-binding proteins – Enzyme structure – Genetic causes of cancer – Helicases
Zdroje
1. Cantor SB, Bell DW, Ganesan S, Kass EM, Drapkin R, Grossman S, et al. BACH1, a novel helicase-like protein, interacts directly with BRCA1 and contributes to its DNA repair function. Cell. 2001;105: 149–160. doi: 10.1016/s0092-8674(01)00304-x 11301010
2. Litman R, Peng M, Jin Z, Zhang F, Zhang J, Powell S, et al. BACH1 is critical for homologous recombination and appears to be the Fanconi anemia gene product FANCJ. Cancer Cell. 2005;8: 255–265. doi: 10.1016/j.ccr.2005.08.004 16153896
3. Levitus M, Waisfisz Q, Godthelp BC, De Vries Y, Hussain S, Wiegant WW, et al. The DNA helicase BRIP1 is defective in Fanconi anemia complementation group J. Nat Genet. 2005;37: 934–935. doi: 10.1038/ng1625 16116423
4. Levran O, Attwooll C, Henry RT, Milton KL, Neveling K, Rio P, et al. The BRCA1-interacting helicase BRIP1 is deficient in Fanconi anemia. Nat Genet. 2005;37: 931 933. doi: 10.1038/ng1624 16116424
5. Bridge WL, Vandenberg CJ, Franklin RJ, Hiom K. The BRIP1 helicase functions independently of BRCA1 in the Fanconi anemia pathway for DNA crosslink repair. Nat Genet. 2005;37: 953–957. doi: 10.1038/ng1627 16116421
6. Nalepa G, Clapp DW. Fanconi anaemia and cancer: An intricate relationship. Nat Rev Cancer. 2018;18: 168–185. doi: 10.1038/nrc.2017.116 29376519
7. Ceccaldi R, Sarangi P, D’Andrea AD. The Fanconi anaemia pathway: new players and new functions. Nat Rev Mol Cell Biol. 2016;17: 337–349. doi: 10.1038/nrm.2016.48 27145721
8. Peng M, Litman R, Xie J, Sharma S, Brosh RM, Cantor SB. The FANCJ/MutLα interaction is required for correction of the cross-link response in FA-J cells. EMBO J. 2007;26: 3238–3249. doi: 10.1038/sj.emboj.7601754 17581638
9. Castillo Bosch P, Segura‐Bayona S, Koole W, Heteren JT, Dewar JM, Tijsterman M, et al. FANCJ promotes DNA synthesis through G-quadruplex structures. EMBO J. 2014;33: 2521–2533. doi: 10.15252/embj.201488663 25193968
10. Sarkies P, Murat P, Phillips LG, Patel KJ, Balasubramanian S, Sale JE. FANCJ coordinates two pathways that maintain epigenetic stability at G-quadruplex DNA. Nucleic Acids Res. 2012;40: 1485–1498. doi: 10.1093/nar/gkr868 22021381
11. Schwab RA, Nieminuszczy J, Shin-ya K, Niedzwiedz W. FANCJ couples replication past natural fork barriers with maintenance of chromatin structure. J Cell Biol. 2013;201: 33–48. doi: 10.1083/jcb.201208009 23530069
12. Wu Y, Shin-ya K, Brosh RM. FANCJ Helicase Defective in Fanconia Anemia and Breast Cancer Unwinds G-Quadruplex DNA To Defend Genomic Stability. Mol Cell Biol. 2008;28: 4116–4128. doi: 10.1128/MCB.02210-07 18426915
13. Cheung I, Schertzer M, Rose A, Lansdorp PM. Disruption of dog-1 in Caenorhabditis elegans triggers deletions upstream of guanine-rich DNA. Nat Genet. 2002;31: 405–409. doi: 10.1038/ng928 12101400
14. London TBC, Barber LJ, Mosedale G, Kelly GP, Balasubramanian S, Hickson ID, et al. FANCJ is a structure-specific DNA helicase associated with the maintenance of genomic G/C tracts. J Biol Chem. 2008;283: 36132–36139. doi: 10.1074/jbc.M808152200 18978354
15. Gupta R, Sharma S, Sommers JA, Jin Z, Cantor SB, Brosh RM. Analysis of the DNA Substrate Specificity of the Human BACH1 Helicase Associated with Breast Cancer. J Biol Chem. 2005;280: 25450–25460. doi: 10.1074/jbc.M501995200 15878853
16. Rudolf J, Makrantoni V, Ingledew WJ, Stark MJR, White MF. The DNA Repair Helicases XPD and FancJ Have Essential Iron-Sulfur Domains. Mol Cell. 2006;23: 801–808. doi: 10.1016/j.molcel.2006.07.019 16973432
17. Liu H, Rudolf J, Johnson KA, McMahon SA, Oke M, Carter L, et al. Structure of the DNA Repair Helicase XPD. Cell. 2008;133: 801–812. doi: 10.1016/j.cell.2008.04.029 18510925
18. Fan L, Fuss JO, Cheng QJ, Arvai AS, Hammel M, Roberts VA, et al. XPD Helicase Structures and Activities: Insights into the Cancer and Aging Phenotypes from XPD Mutations. Cell. 2008;133: 789–800. doi: 10.1016/j.cell.2008.04.030 18510924
19. Wolski SC, Kuper J, Hänzelmann P, Truglio JJ, Croteau DL, Van Houten B, et al. Crystal structure of the FeS cluster-containing nucleotide excision repair helicase XPD. PLoS Biol. 2008;6: 1332–1342. doi: 10.1371/journal.pbio.0060149 18578568
20. Wu Y, Sommers JA, Suhasini AN, Leonard T, Deakyne JS, Mazin AV., et al. Fanconi anemia group J mutation abolishes its DNA repair function by uncoupling DNA translocation from helicase activity or disruption of protein-DNA complexes. Blood. 2010;116: 3780–3791. doi: 10.1182/blood-2009-11-256016 20639400
21. Cantor S, Drapkin R, Zhang F, Lin Y, Han J, Pamidi S, et al. The BRCA1-associated protein BACH1 is a DNA helicase targeted by clinically relevant inactivating mutations. Proc Natl Acad Sci U S A. 2004;101: 2357–2362. doi: 10.1073/pnas.0308717101 14983014
22. Kim H, Cho D-Y, Choi DH, Jung GH, Shin I, Park W, et al. Analysis of BRIP1 Variants among Korean Patients with BRCA1/2 Mutation-Negative High-Risk Breast Cancer. Cancer Res Treat. 2016;48: 955–961. doi: 10.4143/crt.2015.191 26790966
23. Paulo P, Maia S, Pinto C, Pinto P, Monteiro A, Peixoto A, et al. Targeted next generation sequencing identifies functionally deleterious germline mutations in novel genes in early-onset/familial prostate cancer. PLoS Genet. 2018;14: e1007355. doi: 10.1371/journal.pgen.1007355 29659569
24. Gupta R, Sharma S, Sommers JA, Kenny MK, Cantor SB, Brosh RM. FANCJ (BACH1) helicase forms DNA damage inducible foci with replication protein a and interacts physically and functionally with the single-stranded DNA-binding protein. Blood. 2007;110: 2390–2398. doi: 10.1182/blood-2006-11-057273 17596542
25. Dubaele S, De Santis LP, Bienstock RJ, Keriel A, Stefanini M, Van Houten B, et al. Basal Transcription Defect Discriminates between Xeroderma Pigmentosum and Trichothiodystrophy in XPD Patients. Mol Cell. 2003;11: 1635–1646. doi: 10.1016/s1097-2765(03)00182-5 12820975
26. Capo-Chichi J, Bharti SK, Sommers JA, Yammine T, Chouery E, Patry L, et al. Identification and Biochemical Characterization of a Novel Mutation in DDX11 Causing Warsaw Breakage Syndrome. Hum Mutat. 2013;34: 103–107. doi: 10.1002/humu.22226 23033317
27. Simon AK, Kummer S, Wild S, Lezaja A, Teloni F, Jozwiakowski SK, et al. The iron-sulfur helicase DDX11 promotes the generation of single-stranded DNA for CHK1 activation. Life Sci alliance. 2020;3: e201900547. doi: 10.26508/lsa.201900547 32071282
28. Gupta R, Sharma S, Doherty KM, Sommers JA, Cantor SB, Brosh RM. Inhibition of BACH1 (FANCJ) helicase by backbone discontinuity is overcome by increased motor ATPase or length of loading strand. Nucleic Acids Res. 2006;34: 6673–6683. doi: 10.1093/nar/gkl964 17145708
29. Yin Y, Lee WTC, Rothenberg E. Ultrafast data mining of molecular assemblies in multiplexed high-density super-resolution images. Nat Commun. 2019;10: 119. doi: 10.1038/s41467-018-08048-2 30631072
30. Rodriguez R, Müller S, Yeoman JA, Trentesaux C, Riou JF, Balasubramanian S. A novel small molecule that alters shelterin integrity and triggers a DNA-damage response at telomeres. J Am Chem Soc. 2008;130: 15758–15759. doi: 10.1021/ja805615w 18975896
31. Smirnov I, Shafer RH. Effect of loop sequence and size on DNA aptamer stability. Biochemistry. 2000;39: 1462–1468. doi: 10.1021/bi9919044 10684628
32. Hazel P, Huppert J, Balasubramanian S, Neidle S. Loop-length-dependent folding of G-quadruplexes. J Am Chem Soc. 2004;126: 16405–16415. doi: 10.1021/ja045154j 15600342
33. Rachwal PA, Brown T, Fox KR. Sequence effects of single base loops in intramolecular quadruplex DNA. FEBS Lett. 2007;581: 1657–1660. doi: 10.1016/j.febslet.2007.03.040 17399710
34. McLuckie KIE, Di Antonio M, Zecchini H, Xian J, Caldas C, Krippendorff BF, et al. G-quadruplex DNA as a molecular target for induced synthetic lethality in cancer cells. J Am Chem Soc. 2013;135: 9640–9643. doi: 10.1021/ja404868t 23782415
35. Zimmer J, Tacconi EMC, Folio C, Badie S, Porru M, Klare K, et al. Targeting BRCA1 and BRCA2 Deficiencies with G-Quadruplex-Interacting Compounds. Mol Cell. 2016;61: 449–460. doi: 10.1016/j.molcel.2015.12.004 26748828
36. Hänsel-Hertsch R, Di Antonio M, Balasubramanian S. DNA G-quadruplexes in the human genome: Detection, functions and therapeutic potential. Nat Rev Mol Cell Biol. 2017;18: 279–284. doi: 10.1038/nrm.2017.3 28225080
37. Drygin D, Lin A, Bliesath J, Ho CB, O’Brien SE, Proffitt C, et al. Targeting RNA polymerase I with an oral small molecule CX-5461 inhibits ribosomal RNA synthesis and solid tumor growth. Cancer Res. 2011;71: 1418–1430. doi: 10.1158/0008-5472.CAN-10-1728 21159662
38. Xu H, Di Antonio M, McKinney S, Mathew V, Ho B, O’Neil NJ, et al. CX-5461 is a DNA G-quadruplex stabilizer with selective lethality in BRCA1/2 deficient tumours. Nat Commun. 2017;8: 14432. doi: 10.1038/ncomms14432 28211448
39. Gong Z, Kim J-E, Leung CCY, Glover JNM, Chen J. BACH1/FANCJ Acts with TopBP1 and Participates Early in DNA Replication Checkpoint Control. Mol Cell. 2010;37: 438–446. doi: 10.1016/j.molcel.2010.01.002 20159562
40. Pipier A, Bossaert M, Riou JF, Noirot C, Nguyễn L-T, Serre R-F, et al. Transcription-associated topoisomerase activities control DNA-breaks production by G-quadruplex ligands. bioRxiv. 2020; 2020.02.18.953851. doi: 10.1101/2020.02.18.953851
41. Olivieri M, Cho T, Álvarez-Quilón A, Li K, Schellenberg MJ, Zimmermann M, et al. A genetic map of the response to DNA damage in human cells. bioRxiv. 2019; 845446. doi: 10.1101/845446
42. Bruno PM, Lu M, Dennis KA, Inam H, Moore CJ, Sheehe J, et al. The primary mechanism of cytotoxicity of the chemotherapeutic agent CX-5461 is topoisomerase II poisoning. Proc Natl Acad Sci U S A. 2020;117: 4053–4060. doi: 10.1073/pnas.1921649117 32041867
43. Jozwiakowski SK, Kummer S, Gari K. Human DNA polymerase delta requires an iron–sulfur cluster for high-fidelity DNA synthesis. Life Sci Alliance. 2019;2: e201900321. doi: 10.26508/lsa.201900321 31278166
44. Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9: 671–675. doi: 10.1038/nmeth.2089 22930834
45. Tighe A, Staples O, Taylor S. Mps1 kinase activity restrains anaphase during an unperturbed mitosis and targets Mad2 to kinetochores. J Cell Biol. 2008;181: 893–901. doi: 10.1083/jcb.200712028 18541701
46. Muñoz IM, Szyniarowski P, Toth R, Rouse J, Lachaud C. Improved Genome Editing in Human Cell Lines Using the CRISPR Method. PLoS One. 2014;9: e109752. doi: 10.1371/journal.pone.0109752 25303670
47. Guzmán C, Bagga M, Kaur A, Westermarck J, Abankwa D. ColonyArea: An ImageJ plugin to automatically quantify colony formation in clonogenic assays. Rota R, editor. PLoS One. 2014;9: e92444. doi: 10.1371/journal.pone.0092444 24647355
48. Huang F, Hartwich TMP, Rivera-Molina FE, Lin Y, Duim WC, Long JJ, et al. Video-rate nanoscopy using sCMOS camera-specific single-molecule localization algorithms. Nat Methods. 2013;10: 653–658. doi: 10.1038/nmeth.2488 23708387
49. Holden SJ, Uphoff S, Kapanidis AN. DAOSTORM: An algorithm for high-density super-resolution microscopy. Nat Methods. 2011;8: 279–280. doi: 10.1038/nmeth0411-279 21451515
50. Yin Y, Rothenberg E. Probing the spatial organization of molecular complexes using triple-pair-correlation. Sci Rep. 2016;6: 30819. doi: 10.1038/srep30819 27545293
Článek vyšel v časopise
PLOS Genetics
2020 Číslo 6
- Proč jsou nemocnice nepřítelem spánku? A jak to změnit?
- Dlouhodobá ketodieta může poškozovat naše orgány
- „Jednohubky“ z klinického výzkumu – 2024/42
- Metamizol jako analgetikum první volby: kdy, pro koho, jak a proč?
- Distribuce a lokalizace speciálně upravených exosomů může zefektivnit léčbu svalových dystrofií
Nejčtenější v tomto čísle
- AXR1 affects DNA methylation independently of its role in regulating meiotic crossover localization
- Osteocalcin promotes bone mineralization but is not a hormone
- Super-resolution imaging of RAD51 and DMC1 in DNA repair foci reveals dynamic distribution patterns in meiotic prophase
- Steroid hormones regulate genome-wide epigenetic programming and gene transcription in human endometrial cells with marked aberrancies in endometriosis