CRL4 regulates recombination and synaptonemal complex aggregation in the Caenorhabditis elegans germline

Autoři: Benjamin Alleva aff001;  Sean Clausen aff001;  Emily Koury aff001;  Adam Hefel aff001;  Sarit Smolikove aff001
Působiště autorů: The department of Biology, The University of Iowa, Iowa City, IA, United States of America aff001
Vyšlo v časopise: CRL4 regulates recombination and synaptonemal complex aggregation in the Caenorhabditis elegans germline. PLoS Genet 15(11): e1008486. doi:10.1371/journal.pgen.1008486
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pgen.1008486


To maintain the integrity of the genome, meiotic DNA double strand breaks (DSBs) need to form by the meiosis-specific nuclease Spo11 and be repaired by homologous recombination. One class of products formed by recombination are crossovers, which are required for proper chromosome segregation in the first meiotic division. The synaptonemal complex (SC) is a protein structure that connects homologous chromosomes during meiotic prophase I. The proper assembly of the SC is important for recombination, crossover formation, and the subsequent chromosome segregation. Here we identify the components of Cullin RING E3 ubiquitin ligase 4 (CRL4) that play a role in SC assembly in Caenorhabditis elegans. Mutants of the CRL4 complex (cul-4, ddb-1, and gad-1) show defects in SC assembly manifested in the formation of polycomplexes (PCs), impaired progression of meiotic recombination, and reduction in crossover numbers. PCs that are formed in cul-4 mutants lack the mobile properties of wild type SC, but are likely not a direct target of ubiquitination. In C. elegans, SC assembly does not require recombination and there is no evidence that PC formation is regulated by recombination as well. However, in one cul-4 mutant PC formation is dependent upon early meiotic recombination, indicating that proper assembly of the SC can be diminished by recombination in some scenarios. Lastly, our studies suggest that CUL-4 deregulation leads to transposition of the Tc3 transposable element, and defects in formation of SPO-11-mediated DSBs. Our studies highlight previously unknown functions of CRL4 in C. elegans meiosis and show that CUL-4 likely plays multiple roles in meiosis that are essential for maintaining genome integrity.

Klíčová slova:

Phenotypes – Caenorhabditis elegans – Recombinant proteins – Ubiquitination – Homologous chromosomes – Homologous recombination – Ligases – Meiotic prophase


1. Reichman R, Alleva B, Smolikove S. Prophase I: Preparing Chromosomes for Segregation in the Developing Oocyte. Results Probl Cell Differ. 2017;59: 125–173. doi: 10.1007/978-3-319-44820-6_5 28247048

2. Zickler D, Kleckner N. Recombination, Pairing, and Synapsis of Homologs during Meiosis. Cold Spring Harbor Perspectives in Biology. 2015;7: a016626. doi: 10.1101/cshperspect.a016626 25986558

3. Hillers KJ, Jantsch V, Martinez-Perez E, Yanowitz JL. Meiosis. WormBook. 2017;2017: 1–43. doi: 10.1895/wormbook.1.178.1 26694509

4. Cahoon CK, Hawley RS. Regulating the construction and demolition of the synaptonemal complex. Nature Structural & Molecular Biology. 2016;23: 369–377. doi: 10.1038/nsmb.3208 27142324

5. McKim KS, Green-Marroquin BL, Sekelsky JJ, Chin G, Steinberg C, Khodosh R, et al. Meiotic synapsis in the absence of recombination. Science. 1998;279: 876–878. doi: 10.1126/science.279.5352.876 9452390

6. Dernburg AF, McDonald K, Moulder G, Barstead R, Dresser M, Villeneuve AM. Meiotic recombination in C. elegans initiates by a conserved mechanism and is dispensable for homologous chromosome synapsis. Cell. 1998;94: 387–398. doi: 10.1016/s0092-8674(00)81481-6 9708740

7. Romanienko PJ, Camerini-Otero RD. The mouse Spo11 gene is required for meiotic chromosome synapsis. Molecular Cell. 2000;6: 975–987.

8. Bhuiyan H, Schmekel K. Meiotic chromosome synapsis in yeast can occur without spo11-induced DNA double-strand breaks. Genetics. Genetics; 2004;168: 775–783. doi: 10.1534/genetics.104.029660 15514052

9. Keeney S, Giroux CN, Kleckner N. Meiosis-specific DNA double-strand breaks are catalyzed by Spo11, a member of a widely conserved protein family. Cell. 1997;88: 375–384. doi: 10.1016/s0092-8674(00)81876-0 9039264

10. Moerman DG, Kiff JE, Waterston RH. Germline excision of the transposable element Tc1 in C. elegans. Nucleic Acids Research. Oxford University Press; 1991;19: 5669–5672. doi: 10.1093/nar/19.20.5669 1658738

11. Nassif N, Penney J, Pal S, Engels WR, Gloor GB. Efficient copying of nonhomologous sequences from ectopic sites via P-element-induced gap repair. Molecular and Cellular Biology. American Society for Microbiology (ASM); 1994;14: 1613–1625. doi: 10.1128/mcb.14.3.1613 8114699

12. Sijen T, Plasterk RHA. Transposon silencing in the Caenorhabditis elegans germ line by natural RNAi. Nature. 2003;426: 310–314. doi: 10.1038/nature02107 14628056

13. Das PP, Bagijn MP, Goldstein LD, Woolford JR, Lehrbach NJ, Sapetschnig A, et al. Piwi and piRNAs act upstream of an endogenous siRNA pathway to suppress Tc3 transposon mobility in the Caenorhabditis elegans germline. Molecular Cell. 2008;31: 79–90. doi: 10.1016/j.molcel.2008.06.003 18571451

14. Tóth KF, Pezic D, Stuwe E, Webster A. The piRNA Pathway Guards the Germline Genome Against Transposable Elements. Adv Exp Med Biol. 2016;886: 51–77. doi: 10.1007/978-94-017-7417-8_4 26659487

15. Zetka MC, Kawasaki I, Strome S, Müller F. Synapsis and chiasma formation in Caenorhabditis elegans require HIM-3, a meiotic chromosome core component that functions in chromosome segregation. Genes & Development. 1999;13: 2258–2270.

16. Couteau F, Zetka M. HTP-1 coordinates synaptonemal complex assembly with homolog alignment during meiosis in C. elegans. Genes & Development. 2005;19: 2744–2756. doi: 10.1101/gad.1348205 16291647

17. Martinez-Perez E. HTP-1-dependent constraints coordinate homolog pairing and synapsis and promote chiasma formation during C. elegans meiosis. Genes & Development. 2005;19: 2727–2743. doi: 10.1101/gad.1338505 16291646

18. Goodyer W, Kaitna S, Couteau F, Ward JD, Boulton SJ, Zetka M. HTP-3 Links DSB Formation with Homolog Pairing and Crossing Over during C. elegans Meiosis. Developmental Cell. 2008;14: 263–274. doi: 10.1016/j.devcel.2007.11.016 18267094

19. Smolikov S, Eizinger A, Schild-Prüfert K, Hurlburt A, McDonald K, Engebrecht J, et al. SYP-3 restricts synaptonemal complex assembly to bridge paired chromosome axes during meiosis in Caenorhabditis elegans. Genetics. 2007;176: 2015–2025. doi: 10.1534/genetics.107.072413 17565948

20. Smolikov S, Schild-Prufert K, Colaiacovo MP. A yeast two-hybrid screen for SYP-3 interactors identifies SYP-4, a component required for synaptonemal complex assembly and chiasma formation in Caenorhabditis elegans meiosis. PLoS Genet. Public Library of Science; 2009;5: e1000669. doi: 10.1371/journal.pgen.1000669.t002

21. MacQueen AJ, Colaiácovo MP, McDonald K, Villeneuve AM. Synapsis-dependent and -independent mechanisms stabilize homolog pairing during meiotic prophase in C. elegans. Genes & Development. Cold Spring Harbor Lab; 2002;16: 2428–2442. doi: 10.1101/gad.1011602 12231631

22. Colaiácovo MP, MacQueen AJ, Martinez-Perez E, McDonald K, Adamo A, La Volpe A, et al. Synaptonemal complex assembly in C. elegans is dispensable for loading strand-exchange proteins but critical for proper completion of recombination. Developmental Cell. 2003;5: 463–474. doi: 10.1016/s1534-5807(03)00232-6 12967565

23. Nadarajan S, Lambert TJ, Altendorfer E, Gao J, Blower MD, Waters JC, et al. Polo-like kinase-dependent phosphorylation of the synaptonemal complex protein SYP-4 regulates double-strand break formation through a negative feedback loop. eLife. eLife Sciences Publications Limited; 2017;6: 265. doi: 10.7554/eLife.23437 28346135

24. Pattabiraman D, Roelens B, Woglar A, Villeneuve AM. Meiotic recombination modulates the structure and dynamics of the synaptonemal complex during C. elegans meiosis. Bhalla N, editor. PLoS Genet. 2017;13: e1006670–30. doi: 10.1371/journal.pgen.1006670 28339470

25. Smolikov S, Schild-Prüfert K, Colaiácovo MP. CRA-1 uncovers a double-strand break-dependent pathway promoting the assembly of central region proteins on chromosome axes during C. elegans meiosis. PLoS Genet. Public Library of Science; 2008;4: e1000088. doi: 10.1371/journal.pgen.1000088 18535664

26. Hou C-C, Yang W-X. New insights to the ubiquitin-proteasome pathway (UPP) mechanism during spermatogenesis. Mol Biol Rep. 2013;40: 3213–3230. doi: 10.1007/s11033-012-2397-y 23268313

27. Vujin A, Zetka M. The proteasome enters the meiotic prophase fray. Bioessays. 2017;39. doi: 10.1002/bies.201700038 28590593

28. Burger J, Merlet J, Tavernier N, Richaudeau B, Arnold A, Ciosk R, et al. CRL2LRR-1 E3-Ligase Regulates Proliferation and Progression through Meiosis in the Caenorhabditis elegans Germline. Bhalla N, editor. PLoS Genet. 2013;9: e1003375. doi: 10.1371/journal.pgen.1003375 23555289

29. Yin Y, Lin C, Kim ST, Roig I, Chen H, Liu L, et al. The E3 ubiquitin ligase Cullin 4A regulates meiotic progression in mouse spermatogenesis. Developmental Biology. 2011;356: 51–62. doi: 10.1016/j.ydbio.2011.05.661 21624359

30. Vyas R, Kumar R, Clermont F, Helfricht A, Kalev P, Sotiropoulou P, et al. RNF4 is required for DNA double-strand break repair in vivo. Cell Death and Differentiation. 2013;20: 490–502. doi: 10.1038/cdd.2012.145 23197296

31. Ouyang Y, Kwon YT, An JY, Eller D, Tsai S-C, Diaz-Perez S, et al. Loss of Ubr2, an E3 ubiquitin ligase, leads to chromosome fragility and impaired homologous recombinational repair. Mutat Res. 2006;596: 64–75. doi: 10.1016/j.mrfmmm.2005.12.016 16488448

32. Yamashita K, Shinohara M, Shinohara A. Rad6-Bre1-mediated histone H2B ubiquitylation modulates the formation of double-strand breaks during meiosis. Proc Natl Acad Sci USA. 2004;101: 11380–11385. doi: 10.1073/pnas.0400078101 15280549

33. Ahuja JS, Sandhu R, Mainpal R, Lawson C, Henley H, Hunt PA, et al. Control of meiotic pairing and recombination by chromosomally tethered 26S proteasome. Science. 2017. doi: 10.1126/science.aaf4778 28059715

34. Brockway H, Balukoff N, Dean M, Alleva B, Smolikove S. The CSN/COP9 signalosome regulates synaptonemal complex assembly during meiotic prophase I of Caenorhabditis elegans. PLoS Genet. Public Library of Science; 2014;10: e1004757. doi: 10.1371/journal.pgen.1004757 25375142

35. Jackson S, Xiong Y. CRL4s: the CUL4-RING E3 ubiquitin ligases. Trends Biochem Sci. 2009;34: 562–570. doi: 10.1016/j.tibs.2009.07.002 19818632

36. Lee J, Zhou P. DCAFs, the missing link of the CUL4-DDB1 ubiquitin ligase. Molecular Cell. 2007;26: 775–780. doi: 10.1016/j.molcel.2007.06.001 17588513

37. Banks D, Wu M, Higa LA, Gavrilova N, Quan J, Ye T, et al. L2DTL/CDT2 and PCNA interact with p53 and regulate p53 polyubiquitination and protein stability through MDM2 and CUL4A/DDB1 complexes. cc. 2006;5: 1719–1729. doi: 10.4161/cc.5.15.3150 16861890

38. Zhong W, Feng H, Santiago FE, Kipreos ET. CUL-4 ubiquitin ligase maintains genome stability by restraining DNA-replication licensing. Nature. 2003;423: 885–889. doi: 10.1038/nature01747 12815436

39. Kim J, Feng H, Kipreos ET. C. elegans CUL-4 prevents rereplication by promoting the nuclear export of CDC-6 via a CKI-1-dependent pathway. Curr Biol. 2007;17: 966–972. doi: 10.1016/j.cub.2007.04.055 17509881

40. Kim Y, Kipreos ET. The Caenorhabditis elegans Replication Licensing Factor CDT-1 Is Targeted for Degradation by the CUL-4/DDB-1 Complex. Molecular and Cellular Biology. 2007;27: 1394–1406. doi: 10.1128/MCB.00736-06 17145765

41. Kopanja D, Roy N, Stoyanova T, Hess RA, Bagchi S, Raychaudhuri P. Cul4A is essential for spermatogenesis and male fertility. Developmental Biology. 2011;352: 278–287. doi: 10.1016/j.ydbio.2011.01.028 21291880

42. Jahns MT, Vezon D, Chambon A, Pereira L, Falque M, Martin OC, et al. Crossover Localisation Is Regulated by the Neddylation Posttranslational Regulatory Pathway. Lichten M, editor. 2014;12: e1001930. doi: 10.1371/journal.pbio.1001930 25116939

43. Kim J, Kipreos ET. Control of the Cdc6 replication licensing factor in metazoa: the role of nuclear export and the CUL4 ubiquitin ligase. cc. 2008;7: 146–150. doi: 10.4161/cc.7.2.5282 18256526

44. Sasagawa Y, Sato S, Ogura T, Higashitani A.C. elegans RBX-2-CUL-5- and RBX-1-CUL-2-based complexes are redundant for oogenesis and activation of the MAP kinase MPK-1. 2007;581: 145–150. doi: 10.1016/j.febslet.2006.12.009 17184777

45. Jia L, Bickel JS, Wu J, Morgan MA, Li H, Yang J, et al. RBX1 (RING box protein 1) E3 ubiquitin ligase is required for genomic integrity by modulating DNA replication licensing proteins. Journal of Biological Chemistry. 2011;286: 3379–3386. doi: 10.1074/jbc.M110.188425 21115485

46. Bosu DR, Feng H, Min K, Kim Y, Wallenfang MR, Kipreos ET. C. elegans CAND-1 regulates cullin neddylation, cell proliferation and morphogenesis in specific tissues. Developmental Biology. Elsevier Inc; 2010;346: 113–126. doi: 10.1016/j.ydbio.2010.07.020 20659444

47. Merritt C, Rasoloson D, Ko D, Seydoux G. 3' UTRs are the primary regulators of gene expression in the C. elegans germline. 2008;18: 1476–1482. doi: 10.1016/j.cub.2008.08.013 18818082

48. Rog O, Köhler S, Dernburg AF. The synaptonemal complex has liquid crystalline properties and spatially regulates meiotic recombination factors. eLife. eLife Sciences Publications Limited; 2017;6: 4482. doi: 10.7554/eLife.21455 28045371

49. Sato A, Isaac B, Phillips CM, Rillo R, Carlton PM, Wynne DJ, et al. Cytoskeletal forces span the nuclear envelope to coordinate meiotic chromosome pairing and synapsis. Cell. 2009;139: 907–919. doi: 10.1016/j.cell.2009.10.039 19913287

50. Alleva B, Balukoff N, Peiper A, Smolikove S. Regulating chromosomal movement by the cochaperone FKB-6 ensures timely pairing and synapsis. The Journal of Cell Biology. Rockefeller University Press; 2017;155: jcb.201606126–22. doi: 10.1083/jcb.201606126 28077446

51. Phillips CM, Wong C, Bhalla N, Carlton PM, Weiser P, Meneely PM, et al. HIM-8 binds to the X chromosome pairing center and mediates chromosome-specific meiotic synapsis. Cell. 2005;123: 1051–1063. doi: 10.1016/j.cell.2005.09.035 16360035

52. Penkner A, Tang L, Novatchkova M, Ladurner M, Fridkin A, Gruenbaum Y, et al. The nuclear envelope protein Matefin/SUN-1 is required for homologous pairing in C. elegans meiosis. Developmental Cell. 2007;12: 873–885. doi: 10.1016/j.devcel.2007.05.004 17543861

53. Kelly KO, Dernburg AF, Stanfield GM, Villeneuve AM. Caenorhabditis elegans msh-5 is required for both normal and radiation-induced meiotic crossing over but not for completion of meiosis. Genetics. Genetics Society of America; 2000;156: 617–630. 11014811

54. Mets DG, Meyer BJ. Condensins regulate meiotic DNA break distribution, thus crossover frequency, by controlling chromosome structure. Cell. 2009;139: 73–86. doi: 10.1016/j.cell.2009.07.035 19781752

55. Ketting RF, Haverkamp TH, van Luenen HG, Plasterk RH. Mut-7 of C. elegans, required for transposon silencing and RNA interference, is a homolog of Werner syndrome helicase and RNaseD. Cell. 1999;99: 133–141. doi: 10.1016/s0092-8674(00)81645-1 10535732

56. Mori I, Moerman DG, Waterston RH. Analysis of a mutator activity necessary for germline transposition and excision of Tc1 transposable elements in Caenorhabditis elegans. Genetics. Genetics Society of America; 1988;120: 397–407. 2848746

57. Bessereau J-L. Transposons in C. elegans. WormBook. 2006;: 1–13. doi: 10.1895/wormbook.1.70.1 18023126

58. Emmons SW, Yesner L. High-frequency excision of transposable element Tc 1 in the nematode Caenorhabditis elegans is limited to somatic cells. Cell. 1984;36: 599–605. doi: 10.1016/0092-8674(84)90339-8 6321037

59. Yokoo R, Zawadzki KA, Nabeshima K, Drake M, Arur S, Villeneuve AM. COSA-1 reveals robust homeostasis and separable licensing and reinforcement steps governing meiotic crossovers. Cell. Elsevier; 2012;149: 75–87. doi: 10.1016/j.cell.2012.01.052 22464324

60. Bilgir C, Dombecki CR, Chen PF, Villeneuve AM, Nabeshima K. Assembly of the Synaptonemal Complex is a Highly Temperature-Sensitive Process that is Supported by PGL-1 during Caenorhabditis elegans Meiosis. G3: Genes|Genomes|Genetics. 2013. doi: doi:10.1534/g3.112.005165

61. Sym M, Roeder GS. Zip1-induced changes in synaptonemal complex structure and polycomplex assembly. The Journal of Cell Biology. The Rockefeller University Press; 1995;128: 455–466. doi: 10.1083/jcb.128.4.455 7860625

62. Costa Y, Speed R, Öllinger R, Alsheimer M, Semple CA, Gautier P, et al. Two novel proteins recruited by synaptonemal complex protein 1 (SYCP1) are at the centre of meiosis. Journal of Cell Science. 2005;118: 2755–2762. doi: 10.1242/jcs.02402 15944401

63. Öllinger R, Alsheimer M, Benavente R. Mammalian protein SCP1 forms synaptonemal complex-like structures in the absence of meiotic chromosomes. Molecular Biology of the Cell. 2005;16: 212–217. doi: 10.1091/mbc.E04-09-0771 15496453

64. Merritt C, Seydoux G. The Puf RNA-binding proteins FBF-1 and FBF-2 inhibit the expression of synaptonemal complex proteins in germline stem cells. Development. 2010;137: 1787–1798. doi: 10.1242/dev.050799 20431119

65. Cheng C-H, Lo Y-H, Liang S-S, Ti S-C, Lin F-M, Yeh C-H, et al. SUMO modifications control assembly of synaptonemal complex and polycomplex in meiosis of Saccharomyces cerevisiae. Genes & Development. 2006;20: 2067–2081. doi: 10.1101/gad.1430406 16847351

66. Hooker GW, Roeder GS. A Role for SUMO in meiotic chromosome synapsis. Curr Biol. 2006;16: 1238–1243. doi: 10.1016/j.cub.2006.04.045 16782016

67. Voelkel-Meiman K, Taylor LF, Mukherjee P, Humphryes N, Tsubouchi H, MacQueen AJ. SUMO localizes to the central element of synaptonemal complex and is required for the full synapsis of meiotic chromosomes in budding yeast. PLoS Genet. 2013;9: e1003837. doi: 10.1371/journal.pgen.1003837 24098146

68. Rao HBDP, Qiao H, Bhatt SK, Bailey LRJ, Tran HD, Bourne SL, et al. A SUMO-ubiquitin relay recruits proteasomes to chromosome axes to regulate meiotic recombination. Science. 2017. doi: 10.1126/science.aaf6407 28059716

69. Bhalla N, Wynne DJ, Jantsch V, Dernburg AF. ZHP-3 acts at crossovers to couple meiotic recombination with synaptonemal complex disassembly and bivalent formation in C. elegans. PLoS Genet. 2008;4: e1000235. doi: 10.1371/journal.pgen.1000235 18949042

70. Reichman R, Shi Z, Malone R, Smolikove S. Mitotic and Meiotic Functions for the SUMOylation Pathway in the Caenorhabditis elegans Germline. Genetics. 2018;208: 1421–1441. doi: 10.1534/genetics.118.300787 29472245

71. Gao J, Barroso C, Zhang P, Kim H-M, Li S, Labrador L, et al. N-terminal acetylation promotes synaptonemal complex assembly in C. elegans. Genes & Development. Cold Spring Harbor Lab; 2016;30: 2404–2416. doi: 10.1101/gad.277350.116 27881602

72. Sato-Carlton A, Nakamura-Tabuchi C, Chartrand SK, Uchino T, Carlton PM. Phosphorylation of the synaptonemal complex protein SYP-1 promotes meiotic chromosome segregation. The Journal of Cell Biology. 2018;217: 555–570. doi: 10.1083/jcb.201707161 29222184

73. Petroski MD, Deshaies RJ. Function and regulation of cullin-RING ubiquitin ligases. Nat Rev Mol Cell Biol. 2005;6: 9–20. doi: 10.1038/nrm1547 15688063

74. Bosu DR, Kipreos ET. Cullin-RING ubiquitin ligases: global regulation and activation cycles. Cell Division. 2008;3: 7. doi: 10.1186/1747-1028-3-7 18282298

75. Smolikov S, Eizinger A, Hurlburt A, Rogers E, Villeneuve AM, Colaiacovo MP. Synapsis-Defective Mutants Reveal a Correlation Between Chromosome Conformation and the Mode of Double-Strand Break Repair During Caenorhabditis elegans Meiosis. Genetics. 2007;176: 2027–2033. doi: 10.1534/genetics.107.076968 17565963

76. Molinier J, Lechner E, Dumbliauskas E, Genschik P. Regulation and role of Arabidopsis CUL4-DDB1A-DDB2 in maintaining genome integrity upon UV stress. PLoS Genet. 2008;4: e1000093. doi: 10.1371/journal.pgen.1000093 18551167

77. Scrima A, Koníčková R, Czyzewski BK, Kawasaki Y, Jeffrey PD, Groisman R, et al. Structural Basis of UV DNA-Damage Recognition by the DDB1-DDB2 Complex. Cell. Elsevier Ltd; 2008;135: 1213–1223. doi: 10.1016/j.cell.2008.10.045 19109893

78. Wang H, Zhai L, Xu J, Joo H-Y, Jackson S, Erdjument-Bromage H, et al. Histone H3 and H4 Ubiquitylation by the CUL4-DDB-ROC1 Ubiquitin Ligase Facilitates Cellular Response to DNA Damage. Molecular Cell. 2006;22: 383–394. doi: 10.1016/j.molcel.2006.03.035 16678110

79. Zeng M, Ren L, Mizuno K, Nestoras K, Wang H, Tang Z, et al. CRL4(Wdr70) regulates H2B monoubiquitination and facilitates Exo1-dependent resection. Nat Comms. 2016;7: 11364. doi: 10.1038/ncomms11364 27098497

80. Abbas T, Shibata E, Park J, Jha S, Karnani N, Dutta A. CRL4(Cdt2) regulates cell proliferation and histone gene expression by targeting PR-Set7/Set8 for degradation. Molecular Cell. 2010;40: 9–21. doi: 10.1016/j.molcel.2010.09.014 20932471

81. Leung-Pineda V, Huh J, Piwnica-Worms H. DDB1 targets Chk1 to the Cul4 E3 ligase complex in normal cycling cells and in cells experiencing replication stress. Cancer Research. 2009;69: 2630–2637. doi: 10.1158/0008-5472.CAN-08-3382 19276361

82. Gao J, Kim H-M, Elia AE, Elledge SJ, Colaiácovo MP. NatB domain-containing CRA-1 antagonizes hydrolase ACER-1 linking acetyl-CoA metabolism to the initiation of recombination during C. elegans meiosis. PLoS Genet. Public Library of Science; 2015;11: e1005029. doi: 10.1371/journal.pgen.1005029 25768301

83. Machovina TS, Mainpal R, Daryabeigi A, McGovern O, Paouneskou D, Labella S, et al. A Surveillance System Ensures Crossover Formation in C. elegans. 2016;26: 2873–2884. doi: 10.1016/j.cub.2016.09.007 27720619

84. Wang Y-L, Li Q, Xie J, Zhu M, Sun W-J, He L, et al. Involvement of the single Cul4 gene of Chinese mitten crab Eriocheir sinensis in spermatogenesis. Gene. 2014;536: 9–17. doi: 10.1016/j.gene.2013.11.099 24334119

85. Lampert F, Brodersen MML, Peter M. Guard the guardian: A CRL4 ligase stands watch over histone production. Nucleus. 2017;8: 134–143. doi: 10.1080/19491034.2016.1276143 28072566

86. Paix A, Schmidt H, Seydoux G. Cas9-assisted recombineering in C. elegans: genome editing using in vivo assembly of linear DNAs. Nucleic Acids Research. 2016. doi: 10.1093/nar/gkw502 27257074

87. Kim H, Ishidate T, Ghanta KS, Seth M, Conte D, Shirayama M, et al. A Co-CRISPR Strategy for Efficient Genome Editing in Caenorhabditis elegans. Genetics. Genetics; 2014;197: 1069–1080. doi: 10.1534/genetics.114.166389 24879462

88. Koury E, Harrell K, Smolikove S. Differential RPA-1 and RAD-51 recruitment in vivo throughout the C. elegans germline, as revealed by laser microirradiation. Nucleic Acids Research. 2018;46: 748–764. doi: 10.1093/nar/gkx1243 29244155

89. Kamath RS, Fraser AG, Dong Y, Poulin G, Durbin R, Gotta M, et al. Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature. 2003;421: 231–237. doi: 10.1038/nature01278 12529635

Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics

2019 Číslo 11

Najčítanejšie v tomto čísle

Tejto téme sa ďalej venujú…

Zabudnuté heslo

Nemáte účet?  Registrujte sa

Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.


Nemáte účet?  Registrujte sa