Protein Phosphatase 4 Promotes Chromosome Pairing and Synapsis, and Contributes to Maintaining Crossover Competence with Increasing Age

English version České info

Meiosis creates gametes by distributing diploid genomes containing homologous chromosome pairs into daughter cells that receive only one of each chromosome. To segregate correctly at the first meiotic division, chromosomes must pair and synapse with their homologous partners, and undergo crossover recombination, which requires breaking and repairing the DNA strands of all chromosomes. How chromosomes recognize their partners, and how a cell controls the amount of DNA breakage and recombination that occurs, are open questions. In this study, we observed meiosis in the nematode Caenorhabditis elegans to examine the role of Protein Phosphatase 4 (PP4). We found that in the absence of PP4, chromosomes often paired and synapsed with non-homologous chromosomes, or synapsed with themselves by folding in half. Additionally, without PP4 activity, the number of DNA breaks and of crossover recombination events were both independently reduced. The latter two defects became even worse with increasing age, indicating that older animals require PP4 to a greater extent. These findings shed light on how protein phosphorylation controls meiotic events, and demonstrate unanticipated, important roles for PP4.

Vyšlo v časopise: Protein Phosphatase 4 Promotes Chromosome Pairing and Synapsis, and Contributes to Maintaining Crossover Competence with Increasing Age. PLoS Genet 10(10): e32767. doi:10.1371/journal.pgen.1004638
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004638

Souhrn

Zdroje

1. KeeneyS, GirouxCN, KlecknerN (1997) Meiosis-specific DNA double-strand breaks are catalyzed by Spo11, a member of a widely conserved protein family. Cell 88: 375–384.

2. ZicklerD, KlecknerN (1998) The leptotene-zygotene transition of meiosis. Annu Rev Genet 32: 619–697.

3. DernburgAF, McdonaldK, MoulderG, BarsteadR, DresserM, et al. (1998) Meiotic recombination in C. elegans initiates by a conserved mechanism and is dispensable for homologous chromosome synapsis. Cell 94: 387–398.

4. McKimKS, Green-MarroquinBL, SekelskyJJ, ChinG, SteinbergC, et al. (1998) Meiotic Synapsis in the Absence of Recombination. Science 279: 876–878.

5. ColaiacovoMP (2006) The many facets of SC function during C. elegans meiosis. Chromosoma 115: 195–211.

6. BollenM, GerlichDW, LesageB (2009) Mitotic phosphatases: from entry guards to exit guides. Trends Cell Biol 19: 531–541.

7. PenknerAM, FridkinA, GloggnitzerJ, BaudrimontA, MachacekT, et al. (2009) Meiotic chromosome homology search involves modifications of the nuclear envelope protein Matefin/SUN-1. Cell 139: 920–933.

8. WoglarA, DaryabeigiA, AdamoA, HabacherC, MachacekT, et al. (2013) Matefin/SUN-1 Phosphorylation Is Part of a Surveillance Mechanism to Coordinate Chromosome Synapsis and Recombination with Meiotic Progression and Chromosome Movement. PLOS Genet 9: e1003335.

9. MacQueenAJ, ColaiacovoMP, McDonaldK, VilleneuveAM (2002) Synapsis-dependent and -independent mechanisms stabilize homolog pairing during meiotic prophase in C. elegans. Genes Dev 16: 2428–2442.

10. ColaiácovoMP, MacQueenAJ, Martinez-PerezE, McDonaldK, AdamoA, et al. (2003) Synaptonemal complex assembly in C. elegans is dispensable for loading strand-exchange proteins but critical for proper completion of recombination. Dev Cell 5: 463–474.

11. PhillipsCM, WongC, BhallaN, CarltonPM, WeiserP, et al. (2005) HIM-8 binds to the X chromosome pairing center and mediates chromosome-specific meiotic synapsis. Cell 123: 1051–1063.

12. RosuS, ZawadzkiKA, StamperEL, LibudaDE, ReeseAL, et al. (2013) The C. elegans DSB-2 Protein Reveals a Regulatory Network that Controls Competence for Meiotic DSB Formation and Promotes Crossover Assurance. PLOS Genet 9: e1003674.

13. StamperEL, RodenbuschSE, RosuS, AhringerJ, VilleneuveAM, et al. (2013) Identification of DSB-1, a Protein Required for Initiation of Meiotic Recombination in Caenorhabditis elegans, Illuminates a Crossover Assurance Checkpoint. PLOS Genet 9: e1003679.

14. MacQueenAJ, VilleneuveAM (2001) Nuclear reorganization and homologous chromosome pairing during meiotic prophase require C. elegans chk-2. Genes Dev 15: 1674–1687.

15. Garcia-MuseT, BoultonSJ (2005) Distinct modes of ATR activation after replication stress and DNA double-strand breaks in Caenorhabditis elegans. EMBO J 24: 4345–4355.

16. SumiyoshiE, SugimotoA, YamamotoM (2002) Protein phosphatase 4 is required for centrosome maturation in mitosis and sperm meiosis in C. elegans. J Cell Sci 115: 1403–1410.

17. FalkJE, ChanAC, HoffmannE, HochwagenA (2010) A Mec1- and PP4-dependent checkpoint couples centromere pairing to meiotic recombination. Dev Cell 19: 599–611.

18. GladstoneMN, ObesoD, ChuongH, DawsonDS (2009) The Synaptonemal Complex Protein Zip1 Promotes Bi-Orientation of Centromeres at Meiosis I. PLOS Genet. 5: e1000771.

19. NewnhamL, JordanP, RockmillB, RoederGS, HoffmannE (2010) The synaptonemal complex protein, Zip1, promotes the segregation of nonexchange chromosomes at meiosis I. Proc Natl Acad Sci. 107: 781–785.

20. Martínez-PérezE, ShawP, ReaderS, Aragón-AlcaideL, MillerT, et al. (1999) Homologous chromosome pairing in wheat. J Cell Sci 112 (Pt 11): 1761–1769.

21. TsubouchiT, RoederGS (2005) A synaptonemal complex protein promotes homology-independent centromere coupling. Science 308: 870–873.

22. ZhouG, MihindukulasuriyaKA, MacCorkle-ChosnekRA, HooserAV, HuMC-T, et al. (2002) Protein Phosphatase 4 Is Involved in Tumor Necrosis Factor-α-induced Activation of c-Jun N-terminal Kinase. J Biol Chem 277: 6391–6398.

23. LeeD-H, PanY, KannerS, SungP, BorowiecJA, et al. (2010) A PP4 phosphatase complex dephosphorylates RPA2 to facilitate DNA repair via homologous recombination. Nat Struct Mol Biol 17: 365–372.

24. PhillipsCM, DernburgAF (2006) A family of zinc-finger proteins is required for chromosome-specific pairing and synapsis during meiosis in C. elegans. Dev Cell 11: 817–829.

25. ZicklerD, KlecknerN (1999) Meiotic chromosomes: integrating structure and function. Annu Rev Genet 33: 603–754.

26. GustafssonMGL, ShaoL, CarltonPM, WangRCJ, GolubovskayaIN, et al. (2008) Three-dimensional resolution doubling in wide-field fluorescence microscopy by structured illumination. Biophys J 94: 4957–4970.

27. WangC-JR, CarltonPM, GolubovskayaIN, CandeWZ (2009) Interlock Formation and Coiling of Meiotic Chromosome Axes During Synapsis. Genetics 183: 905–915.

28. CouteauF, NabeshimaK, VilleneuveA, ZetkaM (2004) A component of C. elegans meiotic chromosome axes at the interface of homolog alignment, synapsis, nuclear reorganization, and recombination. Curr Biol CB 14: 585–592.

29. Martinez-PerezE, VilleneuveAM (2005) HTP-1-dependent constraints coordinate homolog pairing and synapsis and promote chiasma formation during C. elegans meiosis. Genes Dev 19: 2727–2743.

30. CouteauF, ZetkaM (2005) HTP-1 coordinates synaptonemal complex assembly with homolog alignment during meiosis in C. elegans. Genes Dev 19: 2744–2756.

31. SmolikovS, EizingerA, Schild-PrufertK, HurlburtA, McDonaldK, et al. (2007) SYP-3 restricts synaptonemal complex assembly to bridge paired chromosome axes during meiosis in Caenorhabditis elegans. Genetics 176: 2015–2025.

32. PenknerA, TangL, NovatchkovaM, LadurnerM, FridkinA, et al. (2007) The nuclear envelope protein Matefin/SUN-1 is required for homologous pairing in C. elegans meiosis. Dev Cell 12: 873–885.

33. SchwachaA, KlecknerN (1997) Interhomolog bias during meiotic recombination: meiotic functions promote a highly differentiated interhomolog-only pathway. Cell 90: 1123–1135.

34. MiyazakiT, BressanDA, ShinoharaM, HaberJE, ShinoharaA (2004) In vivo assembly and disassembly of Rad51 and Rad52 complexes during double-strand break repair. EMBO J 23: 939–949.

35. MetsDG, MeyerBJ (2009) Condensins Regulate Meiotic DNA Break Distribution, thus Crossover Frequency, by Controlling Chromosome Structure. Cell 139: 73–86.

36. SaitoTT, MohideenF, MeyerK, HarperJW, ColaiácovoMP (2012) SLX-1 is required for maintaining genomic integrity and promoting meiotic noncrossovers in the Caenorhabditis elegans germline. PLOS Genet 8: e1002888.

37. YokooR, ZawadzkiKA, NabeshimaK, DrakeM, ArurS, et al. (2012) COSA-1 reveals robust homeostasis and separable licensing and reinforcement steps governing meiotic crossovers. Cell 149: 75–87.

38. BrennerS (1974) The genetics of Caenorhabditis elegans. Genetics 77: 71.

39. MeneelyPM, FaragoAF, KauffmanTM (2002) Crossover distribution and high interference for both the X chromosome and an autosome during oogenesis and spermatogenesis in Caenorhabditis elegans. Genetics 162: 1169–1177.

40. GumiennyTL, LambieE, HartwiegE, HorvitzHR, HengartnerMO (1999) Genetic control of programmed cell death in the Caenorhabditis elegans hermaphrodite germline. Dev Camb Engl 126: 1011–1022.

41. LabellaS, WoglarA, JantschV, ZetkaM (2011) Polo Kinases Establish Links between Meiotic Chromosomes and Cytoskeletal Forces Essential for Homolog Pairing. Dev Cell 21: 948–958.

42. SatoA, IsaacB, PhillipsCM, RilloR, CarltonPM, et al. (2009) Cytoskeletal Forces Span the Nuclear Envelope to Coordinate Meiotic Chromosome Pairing and Synapsis. Cell 139: 907–919.

43. ZhangW, MileyN, ZastrowMS, MacqueenAJ, SatoA, et al. (2012) HAL-2 Promotes Homologous Pairing during Caenorhabditis elegans Meiosis by Antagonizing Inhibitory Effects of Synaptonemal Complex Precursors. PLOS Genet 8: e1002880.

44. O'NeillBM, SzyjkaSJ, LisET, BaileyAO, YatesJR, et al. (2007) Pph3–Psy2 is a phosphatase complex required for Rad53 dephosphorylation and replication fork restart during recovery from DNA damage. Proc Natl Acad Sci 104: 9290–9295.

45. ChuangC-N, ChengY-H, WangT-F (2012) Mek1 stabilizes Hop1-Thr318 phosphorylation to promote interhomolog recombination and checkpoint responses during yeast meiosis. Nucleic Acids Res 40: 11416–11427.

46. FukudaT, PrattoF, SchimentiJC, TurnerJMA, Camerini-OteroRD, et al. (2012) Phosphorylation of chromosome core components may serve as axis marks for the status of chromosomal events during mammalian meiosis. PLOS Genet 8: e1002485.

47. KimJ-A, HicksWM, LiJ, TaySY, HaberJE (2011) Protein phosphatases pph3, ptc2, and ptc3 play redundant roles in DNA double-strand break repair by homologous recombination. Mol Cell Biol 31: 507–516.

48. CarballoJA, PanizzaS, SerrentinoME, JohnsonAL, GeymonatM, et al. (2013) Budding Yeast ATM/ATR Control Meiotic Double-Strand Break (DSB) Levels by Down-Regulating Rec114, an Essential Component of the DSB-machinery. PLOS Genet 9: e1003545.

49. LynnA, AshleyT, HassoldT (2004) Variation in Human Meiotic Recombination. Annu Rev Genomics Hum Genet 5: 317–349.

50. ChengEY, HuntPA, Naluai-CecchiniTA, FlignerCL, FujimotoVY, et al. (2009) Meiotic recombination in human oocytes. PLOS Genet 5: e1000661.

51. Frøkjær-JensenC, DavisMW, HopkinsCE, NewmanBJ, ThummelJM, et al. (2008) Single-copy insertion of transgenes in Caenorhabditis elegans. Nat Genet 40: 1375–1383.

52. MacQueenAJ, PhillipsCM, BhallaN, WeiserP, VilleneuveAM, et al. (2005) Chromosome sites play dual roles to establish homologous synapsis during meiosis in C. elegans. Cell 123: 1037–1050.

53. HarperN, RilloR, Jover-GilS, AssafZ, BhallaN, et al. (2011) Pairing Centers Recruit a Polo-like Kinase to Orchestrate Meiotic Chromosome Dynamics in C. elegans. Dev Cell 21: 934–947.

54. PhillipsCM, McDonaldKL, DernburgAF (2009) Cytological analysis of meiosis in Caenorhabditis elegans. Methods Mol Biol 558: 171–195.