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preLekára.sk / Odborné časopisy / PLOS Genetics / 2015 - 10

FANCI Regulates Recruitment of the FA Core Complex at Sites of DNA Damage Independently of FANCD2

English version České info

Fanconi anemia is a genetic disease characterized by bone marrow failure, congenital malformations and cancer predisposition. Cells derived from Fanconi anemia patients have a dysfunctional FA-BRCA pathway and are deficient in the repair of a specific form of DNA damage, DNA interstrand-crosslinks, that are induced by certain chemotherapeutic drugs. Therefore, the study of FA-BRCA pathway regulation is essential for developing new treatments for Fanconi anemia patients and cancer patients in general. One of the first steps in the pathway is the detection of DNA lesions by the FA core complex. We have optimized a method to visualize the recruitment of the FA core complex to sites of DNA damage and, for the first time, explored how this process occurs. We have uncovered several factors that are required for this recruitment. Among them is a FA core complex substrate, FANCI. We report that non-phosphorylated FANCI, previously believed to be an inactive form, has an important role in the recruitment of the FA core complex and DNA interstrand-crosslink repair. Our findings change the current view of the FA-BRCA pathway and have implications for potential clinical strategies aimed at activating or inhibiting the FA-BRCA pathway.

Vyšlo v časopise: FANCI Regulates Recruitment of the FA Core Complex at Sites of DNA Damage Independently of FANCD2. PLoS Genet 11(10): e32767. doi:10.1371/journal.pgen.1005563
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005563

Souhrn

Fanconi anemia is a genetic disease characterized by bone marrow failure, congenital malformations and cancer predisposition. Cells derived from Fanconi anemia patients have a dysfunctional FA-BRCA pathway and are deficient in the repair of a specific form of DNA damage, DNA interstrand-crosslinks, that are induced by certain chemotherapeutic drugs. Therefore, the study of FA-BRCA pathway regulation is essential for developing new treatments for Fanconi anemia patients and cancer patients in general. One of the first steps in the pathway is the detection of DNA lesions by the FA core complex. We have optimized a method to visualize the recruitment of the FA core complex to sites of DNA damage and, for the first time, explored how this process occurs. We have uncovered several factors that are required for this recruitment. Among them is a FA core complex substrate, FANCI. We report that non-phosphorylated FANCI, previously believed to be an inactive form, has an important role in the recruitment of the FA core complex and DNA interstrand-crosslink repair. Our findings change the current view of the FA-BRCA pathway and have implications for potential clinical strategies aimed at activating or inhibiting the FA-BRCA pathway.

Zdroje

1. Joenje H, Patel KJ. The emerging genetic and molecular basis of Fanconi anaemia. Nature reviews Genetics. 2001;2(6):446–57. Epub 2001/06/05. 11389461

2. Bogliolo M, Schuster B, Stoepker C, Derkunt B, Su Y, Raams A, et al. Mutations in ERCC4, encoding the DNA-repair endonuclease XPF, cause Fanconi anemia. American journal of human genetics. 2013;92(5):800–6. Epub 2013/04/30. doi: 10.1016/j.ajhg.2013.04.002 23623386

3. Kim Y, Lach FP, Desetty R, Hanenberg H, Auerbach AD, Smogorzewska A. Mutations of the SLX4 gene in Fanconi anemia. Nature genetics. 2011;43(2):142–6. Epub 2011/01/18. doi: 10.1038/ng.750 21240275

4. Sawyer SL, Tian L, Kahkonen M, Schwartzentruber J, Kircher M, University of Washington Centre for Mendelian G, et al. Biallelic mutations in BRCA1 cause a new Fanconi anemia subtype. Cancer discovery. 2015;5(2):135–42. Epub 2014/12/05. doi: 10.1158/2159-8290.CD-14-1156 25472942

5. Vaz F, Hanenberg H, Schuster B, Barker K, Wiek C, Erven V, et al. Mutation of the RAD51C gene in a Fanconi anemia-like disorder. Nature genetics. 2010;42(5):406–9. Epub 2010/04/20. doi: 10.1038/ng.570 20400963

6. Wang W. Emergence of a DNA-damage response network consisting of Fanconi anaemia and BRCA proteins. Nature reviews Genetics. 2007;8(10):735–48. Epub 2007/09/05. 17768402

7. Hira A, Yoshida K, Sato K, Okuno Y, Shiraishi Y, Chiba K, et al. Mutations in the gene encoding the E2 conjugating enzyme UBE2T cause Fanconi anemia. American journal of human genetics. 2015;96(6):1001–7. doi: 10.1016/j.ajhg.2015.04.022 26046368

8. Rickman KA, Lach FP, Abhyankar A, Donovan FX, Sanborn EM, Kennedy JA, et al. Deficiency of UBE2T, the E2 Ubiquitin Ligase Necessary for FANCD2 and FANCI Ubiquitination, Causes FA-T Subtype of Fanconi Anemia. Cell reports. 2015;12(1):35–41. doi: 10.1016/j.celrep.2015.06.014 26119737

9. Virts EL, Jankowska A, Mackay C, Glaas MF, Wiek C, Kelich SL, et al. AluY-mediated germline deletion, duplication and somatic stem cell reversion in UBE2T defines a new subtype of Fanconi anemia. Hum Mol Genet. 2015.

10. Kim H, D'Andrea AD. Regulation of DNA cross-link repair by the Fanconi anemia/BRCA pathway. Genes & development. 2012;26(13):1393–408. Epub 2012/07/04.

11. Howlett NG, Taniguchi T, Olson S, Cox B, Waisfisz Q, De Die-Smulders C, et al. Biallelic inactivation of BRCA2 in Fanconi anemia. Science. 2002;297(5581):606–9. Epub 2002/06/18. 12065746

12. Meindl A, Hellebrand H, Wiek C, Erven V, Wappenschmidt B, Niederacher D, et al. Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene. Nature genetics. 2010;42(5):410–4. Epub 2010/04/20. doi: 10.1038/ng.569 20400964

13. Rahman N, Seal S, Thompson D, Kelly P, Renwick A, Elliott A, et al. PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Nature genetics. 2007;39(2):165–7. Epub 2007/01/04. 17200668

14. Medhurst AL, Laghmani el H, Steltenpool J, Ferrer M, Fontaine C, de Groot J, et al. Evidence for subcomplexes in the Fanconi anemia pathway. Blood. 2006;108(6):2072–80. Epub 2006/05/25. 16720839

15. Huang Y, Leung JW, Lowery M, Matsushita N, Wang Y, Shen X, et al. Modularized functions of the Fanconi anemia core complex. Cell reports. 2014;7(6):1849–57. Epub 2014/06/10. doi: 10.1016/j.celrep.2014.04.029 24910428

16. Rajendra E, Oestergaard VH, Langevin F, Wang M, Dornan GL, Patel KJ, et al. The genetic and biochemical basis of FANCD2 monoubiquitination. Molecular cell. 2014;54(5):858–69. Epub 2014/06/07. doi: 10.1016/j.molcel.2014.05.001 24905007

17. Kim JM, Kee Y, Gurtan A, D'Andrea AD. Cell cycle-dependent chromatin loading of the Fanconi anemia core complex by FANCM/FAAP24. Blood. 2008;111(10):5215–22. Epub 2008/01/05. doi: 10.1182/blood-2007-09-113092 18174376

18. Meetei AR, Medhurst AL, Ling C, Xue Y, Singh TR, Bier P, et al. A human ortholog of archaeal DNA repair protein Hef is defective in Fanconi anemia complementation group M. Nature genetics. 2005;37(9):958–63. Epub 2005/08/24. 16116422

19. Meetei AR, de Winter JP, Medhurst AL, Wallisch M, Waisfisz Q, van de Vrugt HJ, et al. A novel ubiquitin ligase is deficient in Fanconi anemia. Nature genetics. 2003;35(2):165–70. Epub 2003/09/16. 12973351

20. Garcia-Higuera I, Taniguchi T, Ganesan S, Meyn MS, Timmers C, Hejna J, et al. Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway. Molecular cell. 2001;7(2):249–62. Epub 2001/03/10. 11239454

21. Smogorzewska A, Matsuoka S, Vinciguerra P, McDonald ER 3rd, Hurov KE, Luo J, et al. Identification of the FANCI protein, a monoubiquitinated FANCD2 paralog required for DNA repair. Cell. 2007;129(2):289–301. Epub 2007/04/07. 17412408

22. Sims AE, Spiteri E, Sims RJ 3rd, Arita AG, Lach FP, Landers T, et al. FANCI is a second monoubiquitinated member of the Fanconi anemia pathway. Nature structural & molecular biology. 2007;14(6):564–7. Epub 2007/04/27.

23. Andreassen PR, D'Andrea AD, Taniguchi T. ATR couples FANCD2 monoubiquitination to the DNA-damage response. Genes & development. 2004;18(16):1958–63. Epub 2004/08/18.

24. Ishiai M, Kitao H, Smogorzewska A, Tomida J, Kinomura A, Uchida E, et al. FANCI phosphorylation functions as a molecular switch to turn on the Fanconi anemia pathway. Nature structural & molecular biology. 2008;15(11):1138–46. Epub 2008/10/22.

25. Polo SE, Jackson SP. Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications. Genes & development. 2011;25(5):409–33. Epub 2011/03/03.

26. Castella M, Pujol R, Callen E, Trujillo JP, Casado JA, Gille H, et al. Origin, functional role, and clinical impact of Fanconi anemia FANCA mutations. Blood. 2011;117(14):3759–69. Epub 2011/01/29. doi: 10.1182/blood-2010-08-299917 21273304

27. Mi J, Kupfer GM. The Fanconi anemia core complex associates with chromatin during S phase. Blood. 2005;105(2):759–66. Epub 2004/07/17. 15256425

28. Sridharan D, Brown M, Lambert WC, McMahon LW, Lambert MW. Nonerythroid alphaII spectrin is required for recruitment of FANCA and XPF to nuclear foci induced by DNA interstrand cross-links. Journal of cell science. 2003;116(Pt 5):823–35. Epub 2003/02/07. 12571280

29. Yan Z, Guo R, Paramasivam M, Shen W, Ling C, Fox D 3rd, et al. A ubiquitin-binding protein, FAAP20, links RNF8-mediated ubiquitination to the Fanconi anemia DNA repair network. Molecular cell. 2012;47(1):61–75. Epub 2012/06/19. doi: 10.1016/j.molcel.2012.05.026 22705371

30. Mailand N, Bekker-Jensen S, Faustrup H, Melander F, Bartek J, Lukas C, et al. RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins. Cell. 2007;131(5):887–900. Epub 2007/11/16. 18001824

31. Escribano-Diaz C, Orthwein A, Fradet-Turcotte A, Xing M, Young JT, Tkac J, et al. A cell cycle-dependent regulatory circuit composed of 53BP1-RIF1 and BRCA1-CtIP controls DNA repair pathway choice. Molecular cell. 2013;49(5):872–83. Epub 2013/01/22. doi: 10.1016/j.molcel.2013.01.001 23333306

32. Feng L, Fong KW, Wang J, Wang W, Chen J. RIF1 counteracts BRCA1-mediated end resection during DNA repair. The Journal of biological chemistry. 2013;288(16):11135–43. Epub 2013/03/15. doi: 10.1074/jbc.M113.457440 23486525

33. Singh TR, Ali AM, Paramasivam M, Pradhan A, Wahengbam K, Seidman MM, et al. ATR-dependent phosphorylation of FANCM at serine 1045 is essential for FANCM functions. Cancer research. 2013;73(14):4300–10. Epub 2013/05/24. doi: 10.1158/0008-5472.CAN-12-3976 23698467

34. Reaper PM, Griffiths MR, Long JM, Charrier JD, Maccormick S, Charlton PA, et al. Selective killing of ATM -⁠ or p53-deficient cancer cells through inhibition of ATR. Nature chemical biology. 2011;7(7):428–30. Epub 2011/04/15. doi: 10.1038/nchembio.573 21490603

35. Longerich S, Kwon Y, Tsai MS, Hlaing AS, Kupfer GM, Sung P. Regulation of FANCD2 and FANCI monoubiquitination by their interaction and by DNA. Nucleic acids research. 2014;42(9):5657–70. doi: 10.1093/nar/gku198 24623813

36. Colnaghi L, Jones MJ, Cotto-Rios XM, Schindler D, Hanenberg H, Huang TT. Patient-derived C-terminal mutation of FANCI causes protein mislocalization and reveals putative EDGE motif function in DNA repair. Blood. 2011;117(7):2247–56. Epub 2010/10/26. doi: 10.1182/blood-2010-07-295758 20971953

37. Liang Q, Dexheimer TS, Zhang P, Rosenthal AS, Villamil MA, You C, et al. A selective USP1-UAF1 inhibitor links deubiquitination to DNA damage responses. Nature chemical biology. 2014;10(4):298–304. Epub 2014/02/18. doi: 10.1038/nchembio.1455 24531842

38. Huang TT, Nijman SM, Mirchandani KD, Galardy PJ, Cohn MA, Haas W, et al. Regulation of monoubiquitinated PCNA by DUB autocleavage. Nature cell biology. 2006;8(4):339–47. Epub 2006/03/15. 16531995

39. Chapman JR, Taylor MR, Boulton SJ. Playing the end game: DNA double-strand break repair pathway choice. Molecular cell. 2012;47(4):497–510. Epub 2012/08/28. doi: 10.1016/j.molcel.2012.07.029 22920291

40. Bunting SF, Callen E, Wong N, Chen HT, Polato F, Gunn A, et al. 53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaks. Cell. 2010;141(2):243–54. Epub 2010/04/07. doi: 10.1016/j.cell.2010.03.012 20362325

41. Di Virgilio M, Callen E, Yamane A, Zhang W, Jankovic M, Gitlin AD, et al. Rif1 prevents resection of DNA breaks and promotes immunoglobulin class switching. Science. 2013;339(6120):711–5. Epub 2013/01/12. doi: 10.1126/science.1230624 23306439

42. Zimmermann M, Lottersberger F, Buonomo SB, Sfeir A, de Lange T. 53BP1 regulates DSB repair using Rif1 to control 5' end resection. Science. 2013;339(6120):700–4. Epub 2013/01/12. doi: 10.1126/science.1231573 23306437

43. Ciccia A, Ling C, Coulthard R, Yan Z, Xue Y, Meetei AR, et al. Identification of FAAP24, a Fanconi anemia core complex protein that interacts with FANCM. Molecular cell. 2007;25(3):331–43. Epub 2007/02/10. 17289582

44. Fox D 3rd, Yan Z, Ling C, Zhao Y, Lee DY, Fukagawa T, et al. The histone-fold complex MHF is remodeled by FANCM to recognize branched DNA and protect genome stability. Cell research. 2014;24(5):560–75. Epub 2014/04/05. doi: 10.1038/cr.2014.42 24699063

45. Zhao Q, Saro D, Sachpatzidis A, Singh TR, Schlingman D, Zheng XF, et al. The MHF complex senses branched DNA by binding a pair of crossover DNA duplexes. Nature communications. 2014;5 : 2987. Epub 2014/01/07. doi: 10.1038/ncomms3987 24390579

46. Dorsman JC, Levitus M, Rockx D, Rooimans MA, Oostra AB, Haitjema A, et al. Identification of the Fanconi anemia complementation group I gene, FANCI. Cellular oncology: the official journal of the International Society for Cellular Oncology. 2007;29(3):211–8. Epub 2007/04/25.

47. Sareen A, Chaudhury I, Adams N, Sobeck A. Fanconi anemia proteins FANCD2 and FANCI exhibit different DNA damage responses during S-phase. Nucleic acids research. 2012;40(17):8425–39. Epub 2012/07/04. 22753026

48. Chaudhury I, Sareen A, Raghunandan M, Sobeck A. FANCD2 regulates BLM complex functions independently of FANCI to promote replication fork recovery. Nucleic acids research. 2013;41(13):6444–59. Epub 2013/05/10. doi: 10.1093/nar/gkt348 23658231

49. Chen YH, Jones MJ, Yin Y, Crist SB, Colnaghi L, Sims RJ 3rd, et al. ATR-mediated phosphorylation of FANCI regulates dormant origin firing in response to replication stress. Molecular cell. 2015;58(2):323–38. Epub 2015/04/07. doi: 10.1016/j.molcel.2015.02.031 25843623

50. Collins NB, Wilson JB, Bush T, Thomashevski A, Roberts KJ, Jones NJ, et al. ATR-dependent phosphorylation of FANCA on serine 1449 after DNA damage is important for FA pathway function. Blood. 2009;113(10):2181–90. Epub 2008/12/26. doi: 10.1182/blood-2008-05-154294 19109555

51. Wilson JB, Yamamoto K, Marriott AS, Hussain S, Sung P, Hoatlin ME, et al. FANCG promotes formation of a newly identified protein complex containing BRCA2, FANCD2 and XRCC3. Oncogene. 2008;27(26):3641–52. Epub 2008/01/24. doi: 10.1038/sj.onc.1211034 18212739

52. Xie J, Kim H, Moreau LA, Puhalla S, Garber J, Al Abo M, et al. RNF4-mediated polyubiquitination regulates the Fanconi anemia/BRCA pathway. The Journal of clinical investigation. 2015. Epub 2015/03/10.

53. Nijman SM, Huang TT, Dirac AM, Brummelkamp TR, Kerkhoven RM, D'Andrea AD, et al. The deubiquitinating enzyme USP1 regulates the Fanconi anemia pathway. Molecular cell. 2005;17(3):331–9. Epub 2005/02/08. 15694335

54. Kim JM, Parmar K, Huang M, Weinstock DM, Ruit CA, Kutok JL, et al. Inactivation of murine Usp1 results in genomic instability and a Fanconi anemia phenotype. Developmental cell. 2009;16(2):314–20. Epub 2009/02/17. doi: 10.1016/j.devcel.2009.01.001 19217432

55. Long DT, Joukov V, Budzowska M, Walter JC. BRCA1 promotes unloading of the CMG helicase from a stalled DNA replication fork. Molecular cell. 2014;56(1):174–85. Epub 2014/09/16. doi: 10.1016/j.molcel.2014.08.012 25219499

56. Taniguchi T, Tischkowitz M, Ameziane N, Hodgson SV, Mathew CG, Joenje H, et al. Disruption of the Fanconi anemia-BRCA pathway in cisplatin-sensitive ovarian tumors. Nature medicine. 2003;9(5):568–74. Epub 2003/04/15. 12692539

57. Duckworth-Rysiecki G, Toji L, Ng J, Clarke C, Buchwald M. Characterization of a simian virus 40-transformed Fanconi anemia fibroblast cell line. Mutation research. 1986;166(2):207–14. Epub 1986/09/01. 3020399

58. Jakobs PM, Sahaayaruban P, Saito H, Reifsteck C, Olson S, Joenje H, et al. Immortalization of four new Fanconi anemia fibroblast cell lines by an improved procedure. Somatic cell and molecular genetics. 1996;22(2):151–7. Epub 1996/03/01. 8782494

59. Nakanishi K, Moran A, Hays T, Kuang Y, Fox E, Garneau D, et al. Functional analysis of patient-derived mutations in the Fanconi anemia gene, FANCG/XRCC9. Experimental hematology. 2001;29(7):842–9. Epub 2001/07/05. 11438206

60. O'Driscoll M, Ruiz-Perez VL, Woods CG, Jeggo PA, Goodship JA. A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome. Nature genetics. 2003;33(4):497–501. Epub 2003/03/18. 12640452

61. Kohli M, Rago C, Lengauer C, Kinzler KW, Vogelstein B. Facile methods for generating human somatic cell gene knockouts using recombinant adeno-associated viruses. Nucleic acids research. 2004;32(1):e3. Epub 2004/01/06. 14704360

62. Fattah KR, Ruis BL, Hendrickson EA. Mutations to Ku reveal differences in human somatic cell lines. DNA repair. 2008;7(5):762–74. Epub 2008/04/05. doi: 10.1016/j.dnarep.2008.02.008 18387344

63. Oh S, Harvey A, Zimbric J, Wang Y, Nguyen T, Jackson PJ, et al. DNA ligase III and DNA ligase IV carry out genetically distinct forms of end joining in human somatic cells. DNA repair. 2014;21 : 97–110. Epub 2014/05/20. doi: 10.1016/j.dnarep.2014.04.015 24837021

64. Jacquemont C, Taniguchi T. Proteasome function is required for DNA damage response and fanconi anemia pathway activation. Cancer research. 2007;67(15):7395–405. Epub 2007/08/03. 17671210

65. Wang Y, Huang JW, Li M, Cavenee WK, Mitchell PS, Zhou X, et al. MicroRNA-138 modulates DNA damage response by repressing histone H2AX expression. Molecular cancer research: MCR. 2011;9(8):1100–11. Epub 2011/06/23. doi: 10.1158/1541-7786.MCR-11-0007 21693595

66. Rogakou EP, Boon C, Redon C, Bonner WM. Megabase chromatin domains involved in DNA double-strand breaks in vivo. The Journal of cell biology. 1999;146(5):905–16. Epub 1999/09/09. 10477747

67. Garcia-Higuera I, Kuang Y, Naf D, Wasik J, D'Andrea AD. Fanconi anemia proteins FANCA, FANCC, and FANCG/XRCC9 interact in a functional nuclear complex. Molecular and cellular biology. 1999;19(7):4866–73. Epub 1999/06/22. 10373536

68. Kupfer GM, Naf D, Suliman A, Pulsipher M, D'Andrea AD. The Fanconi anaemia proteins, FAA and FAC, interact to form a nuclear complex. Nature genetics. 1997;17(4):487–90. Epub 1997/12/17. 9398857

69. Wang X, Kennedy RD, Ray K, Stuckert P, Ellenberger T, D'Andrea AD. Chk1-mediated phosphorylation of FANCE is required for the Fanconi anemia/BRCA pathway. Molecular and cellular biology. 2007;27(8):3098–108. Epub 2007/02/14. 17296736

70. Siddique MA, Nakanishi K, Taniguchi T, Grompe M, D'Andrea AD. Function of the Fanconi anemia pathway in Fanconi anemia complementation group F and D1 cells. Experimental hematology. 2001;29(12):1448–55. Epub 2001/12/26. 11750104

71. Ho GP, Margossian S, Taniguchi T, D'Andrea AD. Phosphorylation of FANCD2 on two novel sites is required for mitomycin C resistance. Molecular and cellular biology. 2006;26(18):7005–15. Epub 2006/09/01. 16943440

72. Xia B, Sheng Q, Nakanishi K, Ohashi A, Wu J, Christ N, et al. Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2. Molecular cell. 2006;22(6):719–29. Epub 2006/06/24. 16793542

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Článek Parent-of-Origin Effects of the Gene on Adiposity in Young Adults
Článek Chromatin-Remodelling Complex NURF Is Essential for Differentiation of Adult Melanocyte Stem Cells
Článek Retinoic Acid Receptors Control Spermatogonia Cell-Fate and Induce Expression of the SALL4A Transcription Factor
Článek A Systems Approach Identifies Essential FOXO3 Functions at Key Steps of Terminal Erythropoiesis
Článek Protein O-Glucosyltransferase 1 (POGLUT1) Promotes Mouse Gastrulation through Modification of the Apical Polarity Protein CRUMBS2
Článek KIF7 Controls the Proliferation of Cells of the Respiratory Airway through Distinct Microtubule Dependent Mechanisms
Článek Integration of Posttranscriptional Gene Networks into Metabolic Adaptation and Biofilm Maturation in
Článek Lateral and End-On Kinetochore Attachments Are Coordinated to Achieve Bi-orientation in Oocytes
Článek Protein Homeostasis Imposes a Barrier on Functional Integration of Horizontally Transferred Genes in Bacteria
Článek A New Method for Detecting Associations with Rare Copy-Number Variants
Článek Histone H2AFX Links Meiotic Chromosome Asynapsis to Prophase I Oocyte Loss in Mammals
Článek The Genomic Aftermath of Hybridization in the Opportunistic Pathogen
Článek A Role for the Chaperone Complex BAG3-HSPB8 in Actin Dynamics, Spindle Orientation and Proper Chromosome Segregation during Mitosis
Článek Establishment of a Developmental Compartment Requires Interactions between Three Synergistic -regulatory Modules
Článek Regulation of Spore Formation by the SpoIIQ and SpoIIIA Proteins
Článek Association of the Long Non-coding RNA Steroid Receptor RNA Activator (SRA) with TrxG and PRC2 Complexes
Článek Alkaline Ceramidase 3 Deficiency Results in Purkinje Cell Degeneration and Cerebellar Ataxia Due to Dyshomeostasis of Sphingolipids in the Brain
Článek ACLY and ACC1 Regulate Hypoxia-Induced Apoptosis by Modulating ETV4 via α-ketoglutarate
Článek Quantitative Differences in Nuclear β-catenin and TCF Pattern Embryonic Cells in .
Článek HENMT1 and piRNA Stability Are Required for Adult Male Germ Cell Transposon Repression and to Define the Spermatogenic Program in the Mouse
Článek Axon Regeneration Is Regulated by Ets–C/EBP Transcription Complexes Generated by Activation of the cAMP/Ca Signaling Pathways
Článek A Phenomic Scan of the Norfolk Island Genetic Isolate Identifies a Major Pleiotropic Effect Locus Associated with Metabolic and Renal Disorder Markers
Článek The Roles of CDF2 in Transcriptional and Posttranscriptional Regulation of Primary MicroRNAs
Článek A Genetic Cascade of Modulates Nucleolar Size and rRNA Pool in
Článek Inter-population Differences in Retrogene Loss and Expression in Humans
Článek Cationic Peptides Facilitate Iron-induced Mutagenesis in Bacteria
Článek EP4 Receptor–Associated Protein in Macrophages Ameliorates Colitis and Colitis-Associated Tumorigenesis
Článek Fungal Infection Induces Sex-Specific Transcriptional Changes and Alters Sexual Dimorphism in the Dioecious Plant
Článek FLCN and AMPK Confer Resistance to Hyperosmotic Stress via Remodeling of Glycogen Stores
Článek MET18 Connects the Cytosolic Iron-Sulfur Cluster Assembly Pathway to Active DNA Demethylation in
Článek Sex Bias and Maternal Contribution to Gene Expression Divergence in Blastoderm Embryos
Článek Transcriptional and Linkage Analyses Identify Loci that Mediate the Differential Macrophage Response to Inflammatory Stimuli and Infection
Článek Mre11 and Blm-Dependent Formation of ALT-Like Telomeres in Ku-Deficient
Článek Genome Wide Identification of SARS-CoV Susceptibility Loci Using the Collaborative Cross
Článek Identification of a Single Strand Origin of Replication in the Integrative and Conjugative Element ICE of
Článek The Type VI Secretion TssEFGK-VgrG Phage-Like Baseplate Is Recruited to the TssJLM Membrane Complex via Multiple Contacts and Serves As Assembly Platform for Tail Tube/Sheath Polymerization
Článek The Dynamic Genome and Transcriptome of the Human Fungal Pathogen and Close Relative
Článek Secondary Structure across the Bacterial Transcriptome Reveals Versatile Roles in mRNA Regulation and Function
Článek ROS-Induced JNK and p38 Signaling Is Required for Unpaired Cytokine Activation during Regeneration
Článek Pelle Modulates dFoxO-Mediated Cell Death in
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PLOS Genetics

2015 Číslo 10
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Autori: doc. MUDr. David Zemánek, Ph.D., MUDr. Anna Chaloupka, Ph.D.
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