Controlling Meiotic Recombinational Repair – Specifying the Roles of ZMMs, Sgs1 and Mus81/Mms4 in Crossover Formation
A critical component of successful reproduction is ensuring that the correct number of chromosomes is distributed to the gametes (i.e. sperm, eggs). Incorrect numbers of chromosomes in our gametes can directly result in infertility, miscarriages and developmental disabilities such as Down syndrome. Gamete production involves meiosis, in which crossovers between parental chromosomes are required to promote proper chromosome segregation. However, other types of recombination can occur that are not productive towards appropriate chromosome segregation. In this study, we examine several genes that are thought to play important roles in crossover (CO) promotion. By interpreting the final recombination products using a sequencing based analysis of all four gametes of an individual meiosis in budding yeast, we can infer the roles of these genes in recombination. We find that one protein, Zip3, can direct biased cleavage of the dHJ intermediate but another protein, Msh4, in the same complex cannot. Moreover, we find that a minor resolvase, Mus81/Mms4 (Eme1) is crucial in limiting chromosome entanglements by suppressing multiple consecutive recombination events from initiating from a single double-strand break (DSB). We favor a model that Mms4 is needed to remove a 3′-flap such that second-end capture of the DSB can occur.
Vyšlo v časopise:
Controlling Meiotic Recombinational Repair – Specifying the Roles of ZMMs, Sgs1 and Mus81/Mms4 in Crossover Formation. PLoS Genet 10(10): e32767. doi:10.1371/journal.pgen.1004690
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1004690
Souhrn
A critical component of successful reproduction is ensuring that the correct number of chromosomes is distributed to the gametes (i.e. sperm, eggs). Incorrect numbers of chromosomes in our gametes can directly result in infertility, miscarriages and developmental disabilities such as Down syndrome. Gamete production involves meiosis, in which crossovers between parental chromosomes are required to promote proper chromosome segregation. However, other types of recombination can occur that are not productive towards appropriate chromosome segregation. In this study, we examine several genes that are thought to play important roles in crossover (CO) promotion. By interpreting the final recombination products using a sequencing based analysis of all four gametes of an individual meiosis in budding yeast, we can infer the roles of these genes in recombination. We find that one protein, Zip3, can direct biased cleavage of the dHJ intermediate but another protein, Msh4, in the same complex cannot. Moreover, we find that a minor resolvase, Mus81/Mms4 (Eme1) is crucial in limiting chromosome entanglements by suppressing multiple consecutive recombination events from initiating from a single double-strand break (DSB). We favor a model that Mms4 is needed to remove a 3′-flap such that second-end capture of the DSB can occur.
Zdroje
1. HassoldT, HuntP (2001) To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet 2: 280–291.
2. AllersT, LichtenM (2001) Differential timing and control of noncrossover and crossover recombination during meiosis. Cell 106: 47–57.
3. HunterN, KlecknerN (2001) The single-end invasion: an asymmetric intermediate at the double-strand break to double-holliday junction transition of meiotic recombination. Cell 106: 59–70.
4. BörnerGV, KlecknerN, HunterN (2004) Crossover/noncrossover differentiation, synaptonemal complex formation, and regulatory surveillance at the leptotene/zygotene transition of meiosis. Cell 117: 29–45.
5. SchwachaA, KlecknerN (1995) Identification of double Holliday junctions as intermediates in meiotic recombination. Cell 83: 783–791.
6. MartiniE, BordeV, LegendreM, AudicS, RegnaultB, et al. (2011) Genome-wide analysis of heteroduplex DNA in mismatch repair-deficient yeast cells reveals novel properties of meiotic recombination pathways. PLoS Genet 7: e1002305.
7. PâquesF, HaberJE (1999) Multiple pathways of recombination induced by double-strand breaks in Saccharomyces cerevisiae. Microbiol Mol Biol Rev 63: 349–404.
8. GilbertsonLA, StahlFW (1996) A Test of the Double-Strand Break Repair Model for Meiotic Recombination in Saccharomyces cerevisiae. Genetics 144: 27–41.
9. McMahillMS, ShamCW, BishopDK (2007) Synthesis-dependent strand annealing in meiosis. PLoS Biol 5: 2589–2601.
10. WuL, HicksonID (2003) The Bloom's syndrome helicase suppresses crossing over during homologous recombination. 426: 870–874.
11. De MuytA, JessopL, KolarE, SourirajanA, ChenJ, et al. (2012) BLM helicase ortholog Sgs1 is a central regulator of meiotic recombination intermediate metabolism. Mol Cell 46: 43–53.
12. SourirajanA, LichtenM (2008) Polo-like kinase Cdc5 drives exit from pachytene during budding yeast meiosis. Genes Dev 22: 2627–2632.
13. ZakharyevichK, TangS, MaU, HunterN (2012) Delineation of joint molecule resolution pathways in meiosis identifies a crossover-specific resolvase. Cell 149: 334–347.
14. CejkaP, PlankJL, BachratiCZ, HicksonID, KowalczykowskiSC (2010) Rmi1 stimulates decatenation of double Holliday junctions during dissolution by Sgs1-Top3. Nat Struct Mol Biol 17: 1377–1382.
15. HicksonID, MankouriHW (2011) Processing of homologous recombination repair intermediates by the Sgs1-Top3-Rmi1 and Mus81-Mms4 complexes. Cell Cycle 10: 3078–3085.
16. BachratiCZ, BortsRH, HicksonID (2006) Mobile D-loops are a preferred substrate for the Bloom's syndrome helicase. Nucleic Acids Res 34: 2269–2279.
17. BugreevDV, YuX, EgelmanEH, MazinAV (2007) Novel pro- and anti-recombination activities of the Bloom's syndrome helicase. Genes Dev 21: 3085–3094.
18. Larsen NB, Hickson ID (2013) DNA Helicases and DNA Motor Proteins. In: Spies M, editor. Advances in Experimental Medicine and Biology. New York, NY: Springer New York, Vol. 973. pp. 161–184.
19. OhSD, LaoJP, HwangPY, TaylorAF, SmithGR, et al. (2007) BLM ortholog, Sgs1, prevents aberrant crossing-over by suppressing formation of multichromatid joint molecules. Cell 130: 259–272.
20. JessopL, RockmillB, RoederGS, LichtenM (2006) Meiotic chromosome synapsis-promoting proteins antagonize the anti-crossover activity of sgs1. PLoS Genet 2: e155.
21. RockmillB, FungJC, BrandaSS, RoederGS (2003) The Sgs1 helicase regulates chromosome synapsis and meiotic crossing over. Curr Biol 13: 1954–1962.
22. LynnA, SoucekR, BörnerGV (2007) ZMM proteins during meiosis: crossover artists at work. Chromosome Res 15: 591–605.
23. BoddyMN, GaillardPH, McDonaldWH, ShanahanP, YatesJR, et al. (2001) Mus81-Eme1 are essential components of a Holliday junction resolvase. Cell 107: 537–548.
24. SmithGR, BoddyMN, ShanahanP, RussellP (2003) Fission yeast Mus81.Eme1 Holliday junction resolvase is required for meiotic crossing over but not for gene conversion. Genetics 165: 2289–2293.
25. de los SantosT, LoidlJ, LarkinB, HollingsworthNM (2001) A role for MMS4 in the processing of recombination intermediates during meiosis in Saccharomyces cerevisiae. Genetics 159: 1511–1525.
26. KaliramanV, MullenJR, FrickeWM, Bastin-ShanowerSA, BrillSJ (2001) Functional overlap between Sgs1-Top3 and the Mms4-Mus81 endonuclease. Genes Dev 15: 2730–2740.
27. Sonntag BrownM, LimE, ChenC, NishantKT, AlaniE (2013) Genetic analysis of mlh3 mutations reveals interactions between crossover promoting factors during meiosis in baker's yeast. G3 (Bethesda) 3: 9–22.
28. HaberJE, HeyerW (2001) The Fuss about Mus81 Minireview. 107: 551–554.
29. SchwartzEK, HeyerW-D (2011) Processing of joint molecule intermediates by structure-selective endonucleases during homologous recombination in eukaryotes. Chromosoma 120: 109–127.
30. de los SantosT, HunterN, LeeC, LarkinB, LoidlJ, et al. (2003) The Mus81/Mms4 Endonuclease Acts Independently of Double-Holliday Junction Resolution to Promote a Distinct Subset of Crossovers During Meiosis in Budding Yeast. 94: 81–94.
31. GaillardP-HL, NoguchiE, ShanahanP, RussellP (2003) The endogenous Mus81-Eme1 complex resolves Holliday junctions by a nick and counternick mechanism. Mol Cell 12: 747–759.
32. OsmanF, DixonJ, DoeCL, WhitbyMC (2003) Generating crossovers by resolution of nicked Holliday junctions: a role for Mus81-Eme1 in meiosis. Mol Cell 12: 761–774.
33. HollingsworthNM, BrillSJ (2004) The Mus81 solution to resolution: generating meiotic crossovers without Holliday junctions. Genes Dev 18: 117–125.
34. AndersonCM, ChenSY, DimonMT, OkeA, DeRisiJL, et al. (2011) ReCombine: a suite of programs for detection and analysis of meiotic recombination in whole-genome datasets. PLoS One 6: e25509.
35. ManceraE, BourgonR, BrozziA, HuberW, SteinmetzLM (2008) High-resolution mapping of meiotic crossovers and non-crossovers in yeast. Nature 454: 479–485.
36. QiJ, WijeratneAJ, TomshoLP, HuY, SchusterSC, et al. (2009) Characterization of meiotic crossovers and gene conversion by whole-genome sequencing in Saccharomyces cerevisiae. BMC Genomics 10: 475.
37. WinzelerEA, RichardsDR, ConwayAR, GoldsteinAL, KalmanS, et al. (1998) Direct allelic variation scanning of the yeast genome. Science (80-) 281: 1194–1197.
38. LiuY, GainesWa, CallenderT, BusyginaV, OkeA, et al. (2014) Down-regulation of Rad51 activity during meiosis in yeast prevents competition with Dmc1 for repair of double-strand breaks. PLoS Genet 10: e1004005.
39. ZakharyevichK, MaY, TangS, HwangPY, BoiteuxS, et al. (2010) Temporally and biochemically distinct activities of Exo1 during meiosis: double-strand break resection and resolution of double Holliday junctions. Mol Cell 40: 1001–1015.
40. ShinoharaM, OhSD, HunterN, ShinoharaA (2008) Crossover assurance and crossover interference are distinctly regulated by the ZMM proteins during yeast meiosis. Nat Genet 40: 299–309.
41. OhSD, LaoJP, TaylorAF, SmithGR, HunterN (2008) RecQ helicase, Sgs1, and XPF family endonuclease, Mus81-Mms4, resolve aberrant joint molecules during meiotic recombination. Mol Cell 31: 324–336.
42. JessopL, LichtenM (2008) Mus81/Mms4 endonuclease and Sgs1 helicase collaborate to ensure proper recombination intermediate metabolism during meiosis. Mol Cell 31: 313–323.
43. ChenSY, TsubouchiT, RockmillB, SandlerJS, RichardsDR, et al. (2008) Global analysis of the meiotic crossover landscape. Dev Cell 15: 401–415.
44. CoïcE, GluckL, FabreF (2000) Evidence for short-patch mismatch repair in Saccharomyces cerevisiae. EMBO J 19: 3408–3417.
45. SnowdenT, AcharyaS, ButzC, BerardiniM, FishelR (2004) hMSH4-hMSH5 recognizes Holliday Junctions and forms a meiosis-specific sliding clamp that embraces homologous chromosomes. Mol Cell 15: 437–451.
46. ThackerD, MohibullahN, ZhuX, KeeneyS (2014) Homologue engagement controls meiotic DNA break number and distribution. Nature 510: 241–246.
47. LongtineMS, McKenzieAIII, DemariniDJ, ShahNG (1998) Additional Modules for Versatile and Economical PCR-based Gene Deletion and Modification in Saccharomyces cerevisiae. 961: 953–961.
48. Chen SY, Fung JC (2011) Mapping of Crossover Sites Using DNA Microarrays. In: Tsubouchi H, editor. DNA Recombination. Methods in Molecular Biology. Totowa, NJ: Humana Press, Vol. 745. pp. 117–134.
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2014 Číslo 10
- 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
- The Master Activator of IncA/C Conjugative Plasmids Stimulates Genomic Islands and Multidrug Resistance Dissemination
- A Splice Mutation in the Gene Causes High Glycogen Content and Low Meat Quality in Pig Skeletal Muscle
- Keratin 76 Is Required for Tight Junction Function and Maintenance of the Skin Barrier
- A Role for Taiman in Insect Metamorphosis