Chromosome organization, dynamics and stability are required for successful passage through cellular generations and transmission of genetic information to offspring. The key components involved are Structural maintenance of chromosomes (SMC) complexes. Cohesin complex ensures proper chromatid alignment, condensin complex chromosome condensation and the SMC5/6 complex is specialized in the maintenance of genome stability. Here we summarize recent knowledge on the composition and molecular functions of SMC5/6 complex. SMC5/6 complex was originally identified based on the sensitivity of its mutants to genotoxic stress but there is increasing number of studies demonstrating its roles in the control of DNA replication, sister chromatid resolution and genomic location-dependent promotion or suppression of homologous recombination. Some of these functions appear to be due to a very dynamic interaction with cohesin or other repair complexes. Studies in Arabidopsis indicate that, besides its canonical function in repair of damaged DNA, the SMC5/6 complex plays important roles in regulating plant development, abiotic stress responses, suppression of autoimmune responses and sexual reproduction.

Institute of Experimental Botany of the Czech Academy of Sciences Centre of the Region Haná for Biotechnological and Agricultural Research Šlechtitelů 31 77900 Olomouc Holice Czech Republic

Max Planck Institute for Plant Breeding Research Carl von Linné Weg 10 50829 Cologne Germany

Zobrazit více v PubMed

Kouzarides T. Chromatin modifications and their function. Cell. 2007;128:693–705. doi: 10.1016/j.cell.2007.02.005. PubMed DOI

Li G., Hall T.C., Holmes-Davis R. Plant chromatin: Development and gene control. Bioessays. 2002;24:234–243. doi: 10.1002/bies.10055. PubMed DOI

Branzei D., Vanoli F., Foiani M. SUMOylation regulates Rad18-mediated template switch. Nature. 2008;456:915–920. doi: 10.1038/nature07587. PubMed DOI

Roy S. Maintenance of genome stability in plants: Repairing DNA double strand breaks and chromatin structure stability. Front. Plant Sci. 2014;5:487. doi: 10.3389/fpls.2014.00487. PubMed DOI PMC

Hu Z.B., Cools T., De Veylder L. Mechanisms used by plants to cope with DNA damage. Annu. Rev. Plant. Biol. 2016;67:439–462. doi: 10.1146/annurev-arplant-043015-111902. PubMed DOI

Willing E.M., Piofczyk T., Albert A., Winkler J.B., Schneeberger K., Pecinka A. UVR2 ensures transgenerational genome stability under simulated natural UV-B in Arabidopsis thaliana. Nat. Commun. 2016;7:13522. doi: 10.1038/ncomms13522. PubMed DOI PMC

Balestrazzi A., Confalonieri M., Macovei A., Dona M., Carbonera D. Genotoxic stress and DNA repair in plants: Emerging functions and tools for improving crop productivity. Plant. Cell Rep. 2011;30:287–295. doi: 10.1007/s00299-010-0975-9. PubMed DOI

De Piccoli G., Torres-Rosell J., Aragon L. The unnamed complex: What do we know about Smc5-Smc6? Chromosome Res. 2009;17:251–263. doi: 10.1007/s10577-008-9016-8. PubMed DOI

Hirano T. At the heart of the chromosome: SMC proteins in action. Nat. Rev. Mol. Cell Biol. 2006;7:311–322. doi: 10.1038/nrm1909. PubMed DOI

Losada A., Hirano T. Dynamic molecular linkers of the genome: The first decade of SMC proteins. Genes Dev. 2005;19:1269–1287. doi: 10.1101/gad.1320505. PubMed DOI

Jeppsson K., Kanno T., Shirahige K., Sjogren C. The maintenance of chromosome structure: Positioning and functioning of SMC complexes. Nat. Rev. Mol. Cell Biol. 2014;15:601–614. doi: 10.1038/nrm3857. PubMed DOI

Uhlmann F. SMC complexes: From DNA to chromosomes. Nat. Rev. Mol. Cell Biol. 2016;17:399–412. doi: 10.1038/nrm.2016.30. PubMed DOI

Kanno T., Berta D.G., Sjogren C. The Smc5/6 complex is an ATP-dependent intermolecular DNA linker. Cell Rep. 2015;12:1471–1482. doi: 10.1016/j.celrep.2015.07.048. PubMed DOI

Sergeant J., Taylor E., Palecek J., Fousteri M., Andrews E.A., Sweeney S., Shinagawa H., Watts F.Z., Lehmann A.R. Composition and architecture of the Schizosaccharomyces pombe Rad18 (Smc5-6) complex. Mol. Cell. Biol. 2005;25:172–184. doi: 10.1128/MCB.25.1.172-184.2005. PubMed DOI PMC

Duan X., Yang Y., Chen Y.H., Arenz J., Rangi G.K., Zhao X., Ye H. Architecture of the Smc5/6 Complex of Saccharomyces cerevisiae Reveals a Unique Interaction between the Nse5-6 Subcomplex and the Hinge Regions of Smc5 and Smc6. J. Biol. Chem. 2009;284:8507–8515. doi: 10.1074/jbc.M809139200. PubMed DOI PMC

Palecek J., Vidot S., Feng M., Doherty A.J., Lehmann A.R. The Smc5-Smc6 DNA repair complex. bridging of the Smc5-Smc6 heads by the KLEISIN, Nse4, and non-Kleisin subunits. J. Biol. Chem. 2006;281:36952–36959. doi: 10.1074/jbc.M608004200. PubMed DOI

Fujioka Y., Kimata Y., Nomaguchi K., Watanabe K., Kohno K. Identification of a novel non-structural maintenance of chromosomes (SMC) component of the SMC5-SMC6 complex involved in DNA repair. J. Biol. Chem. 2002;277:21585–21591. doi: 10.1074/jbc.M201523200. PubMed DOI

McDonald W.H., Pavlova Y., Yates J.R., 3rd, Boddy M.N. Novel essential DNA repair proteins Nse1 and Nse2 are subunits of the fission yeast Smc5-Smc6 complex. J. Biol. Chem. 2003;278:45460–45467. doi: 10.1074/jbc.M308828200. PubMed DOI

Taylor E.M., Copsey A.C., Hudson J.J., Vidot S., Lehmann A.R. Identification of the proteins, including MAGEG1, that make up the human SMC5-6 protein complex. Mol. Cell. Biol. 2008;28:1197–1206. doi: 10.1128/MCB.00767-07. PubMed DOI PMC

Pebernard S., Perry J.J., Tainer J.A., Boddy M.N. Nse1 RING-like domain supports functions of the Smc5-Smc6 holocomplex in genome stability. Mol. Biol. Cell. 2008;19:4099–4109. doi: 10.1091/mbc.E08-02-0226. PubMed DOI PMC

Li G., Zou W., Jian L., Qian J., Deng Y., Zhao J. Non-SMC elements 1 and 3 are required for early embryo and seedling development in Arabidopsis. J. Exp. Bot. 2017;68:1039–1054. doi: 10.1093/jxb/erx016. PubMed DOI PMC

Hudson J.J., Bednarova K., Kozakova L., Liao C., Guerineau M., Colnaghi R., Vidot S., Marek J., Bathula S.R., Lehmann A.R., et al. Interactions between the Nse3 and Nse4 components of the SMC5-6 complex identify evolutionarily conserved interactions between MAGE and EID Families. PLoS ONE. 2011;6:e17270. doi: 10.1371/journal.pone.0017270. PubMed DOI PMC

Zabrady K., Adamus M., Vondrova L., Liao C., Skoupilova H., Novakova M., Jurcisinova L., Alt A., Oliver A.W., Lehmann A.R., et al. Chromatin association of the SMC5/6 complex is dependent on binding of its NSE3 subunit to DNA. Nucleic Acids Res. 2016;44:1064–1079. doi: 10.1093/nar/gkv1021. PubMed DOI PMC

Doyle J.M., Gao J., Wang J., Yang M., Potts P.R. MAGE-RING protein complexes comprise a family of E3 ubiquitin ligases. Mol. Cell. 2010;39:963–974. doi: 10.1016/j.molcel.2010.08.029. PubMed DOI PMC

Chomez P., De Backer O., Bertrand M., De Plaen E., Boon T., Lucas S. An overview of the MAGE gene family with the identification of all human members of the family. Cancer Res. 2001;61:5544–5551. PubMed

Barker P.A., Salehi A. The MAGE proteins: Emerging roles in cell cycle progression, apoptosis, and neurogenetic disease. J. Neurosci. Res. 2002;67:705–712. doi: 10.1002/jnr.10160. PubMed DOI

Weon J.L., Potts P.R. The MAGE protein family and cancer. Curr. Opin. Cell Biol. 2015;37:1–8. doi: 10.1016/j.ceb.2015.08.002. PubMed DOI PMC

Schleiffer A., Kaitna S., Maurer-Stroh S., Glotzer M., Nasmyth K., Eisenhaber F. Kleisins: A superfamily of bacterial and eukaryotic SMC protein partners. Mol. Cell. 2003;11:571–575. doi: 10.1016/S1097-2765(03)00108-4. PubMed DOI

Prakash S., Prakash L. Increased spontaneous mitotic segregation in MMS-sensitive mutants of Saccharomyces cerevisiae. Genetics. 1977;87:229–236. PubMed PMC

Zhao X.L., Blobel G. A SUMO ligase is part of a nuclear multiprotein complex that affects DNA repair and chromosomal organization. Proc. Natl. Acad. Sci. USA. 2005;102:4777–4782. doi: 10.1073/pnas.0500537102. PubMed DOI PMC

Xu P., Yuan D., Liu M., Li C., Liu Y., Zhang S., Yao N., Yang C. AtMMS21, an SMC5/6 complex subunit, is involved in stem cell niche maintenance and DNA damage responses in Arabidopsis roots. Plant. Physiol. 2013;161:1755–1768. doi: 10.1104/pp.112.208942. PubMed DOI PMC

Potts P.R., Yu H. Human MMS21/NSE2 is a SUMO ligase required for DNA repair. Mol. Cell. Biol. 2005;25:7021–7032. doi: 10.1128/MCB.25.16.7021-7032.2005. PubMed DOI PMC

Hay R.T. SUMO: A history of modification. Mol. Cell. 2005;18:1–12. doi: 10.1016/j.molcel.2005.03.012. PubMed DOI

Jalal D., Chalissery J., Hassan A.H. Genome maintenance in Saccharomyces cerevisiae: The role of SUMO and SUMO-targeted ubiquitin ligases. Nucleic Acids Res. 2017;45:2242–2261. doi: 10.1093/nar/gkw1369. PubMed DOI PMC

Andrews E.A., Palecek J., Sergeant J., Taylor E., Lehmann A.R., Watts F.Z. Nse2, a component of the Smc5-6 complex, is a SUMO ligase required for the response to DNA damage. Mol. Cell. Biol. 2005;25:185–196. doi: 10.1128/MCB.25.1.185-196.2005. PubMed DOI PMC

McAleenan A., Cordon-Preciado V., Clemente-Blanco A., Liu I.C., Sen N., Leonard J., Jarmuz A., Aragon L. SUMOylation of the alpha-kleisin subunit of cohesin is required for DNA damage-induced cohesion. Curr. Biol. 2012;22:1564–1575. doi: 10.1016/j.cub.2012.06.045. PubMed DOI

Potts P.R., Yu H. The SMC5/6 complex maintains telomere length in ALT cancer cells through SUMOylation of telomere-binding proteins. Nat. Struct. Mol. Biol. 2007;14:581–590. doi: 10.1038/nsmb1259. PubMed DOI

Potts P.R., Porteus M.H., Yu H. Human SMC5/6 complex promotes sister chromatid homologous recombination by recruiting the SMC1/3 cohesin complex to double-strand breaks. EMBO J. 2006;25:3377–3388. doi: 10.1038/sj.emboj.7601218. PubMed DOI PMC

Ishida T., Fujiwara S., Miura K., Stacey N., Yoshimura M., Schneider K., Adachi S., Minamisawa K., Umeda M., Sugimoto K. SUMO E3 ligase HIGH PLOIDY2 regulates endocycle onset and meristem maintenance in Arabidopsis. Plant Cell. 2009;21:2284–2297. doi: 10.1105/tpc.109.068072. PubMed DOI PMC

Huang L., Yang S., Zhang S., Liu M., Lai J., Qi Y., Shi S., Wang J., Wang Y., Xie Q., et al. The Arabidopsis SUMO E3 ligase AtMMS21, a homologue of NSE2/MMS21, regulates cell proliferation in the root. Plant J. 2009;60:666–678. doi: 10.1111/j.1365-313X.2009.03992.x. PubMed DOI

Pebernard S., Wohlschlegel J., McDonald W.H., Yates J.R., 3rd, Boddy M.N. The Nse5-Nse6 dimer mediates DNA repair roles of the Smc5-Smc6 complex. Mol. Cell. Biol. 2006;26:1617–1630. doi: 10.1128/MCB.26.5.1617-1630.2006. PubMed DOI PMC

Yan S., Wang W., Marques J., Mohan R., Saleh A., Durrant W.E., Song J., Dong X. Salicylic acid activates DNA damage responses to potentiate plant immunity. Mol. Cell. 2013;52:602–610. doi: 10.1016/j.molcel.2013.09.019. PubMed DOI PMC

Raschle M., Smeenk G., Hansen R.K., Temu T., Oka Y., Hein M.Y., Nagaraj N., Long D.T., Walter J.C., Hofmann K., et al. DNA repair. Proteomics reveals dynamic assembly of repair complexes during bypass of DNA cross-links. Science. 2015;348:1253671. doi: 10.1126/science.1253671. PubMed DOI PMC

Huber A.H., Nelson W.J., Weis W.I. Three-dimensional structure of the armadillo repeat region of beta-catenin. Cell. 1997;90:871–882. doi: 10.1016/S0092-8674(00)80352-9. PubMed DOI

Fousteri M.I., Lehmann A.R. A novel SMC protein complex in Schizosaccharomyces pombe contains the Rad18 DNA repair protein. EMBO J. 2000;19:1691–1702. doi: 10.1093/emboj/19.7.1691. PubMed DOI PMC

Lehmann A.R., Walicka M., Griffiths D.J., Murray J.M., Watts F.Z., McCready S., Carr A.M. The rad18 gene of Schizosaccharomyces pombe defines a new subgroup of the SMC superfamily involved in DNA repair. Mol. Cell. Biol. 1995;15:7067–7080. doi: 10.1128/MCB.15.12.7067. PubMed DOI PMC

Mengiste T., Revenkova E., Bechtold N., Paszkowski J. An SMC-like protein is required for efficient homologous recombination in Arabidopsis. EMBO J. 1999;18:4505–4512. doi: 10.1093/emboj/18.16.4505. PubMed DOI PMC

Santa Maria S.R., Gangavarapu V., Johnson R.E., Prakash L., Prakash S. Requirement of Nse1, a subunit of the Smc5-Smc6 complex, for Rad52-dependent postreplication repair of UV-damaged DNA in Saccharomyces cerevisiae. Mol. Cell. Biol. 2007;27:8409–8418. doi: 10.1128/MCB.01543-07. PubMed DOI PMC

Kegel A., Sjogren C. The Smc5/6 complex: More than repair? Cold Spring Harb. Symp. Quant. Biol. 2010;75:179–187. doi: 10.1101/sqb.2010.75.047. PubMed DOI

Wu N., Yu H. The Smc complexes in DNA damage response. Cell Biosci. 2012;2:5. doi: 10.1186/2045-3701-2-5. PubMed DOI PMC

Potts P.R. The Yin and Yang of the MMS21-SMC5/6 SUMO ligase complex in homologous recombination. DNA Repair. 2009;8:499–506. doi: 10.1016/j.dnarep.2009.01.009. PubMed DOI

Watanabe K., Pacher M., Dukowic S., Schubert V., Puchta H., Schubert I. The STRUCTURAL MAINTENANCE OF CHROMOSOMES 5/6 complex promotes sister chromatid alignment and homologous recombination after DNA damage in Arabidopsis thaliana. Plant Cell. 2009;21:2688–2699. doi: 10.1105/tpc.108.060525. PubMed DOI PMC

Liu C.H., Finke A., Diaz M., Rozhon W., Poppenberger B., Baubec T., Pecinka A. Repair of DNA damage induced by the cytidine analog zebularine requires ATR and ATM in Arabidopsis. Plant Cell. 2015;27:1788–1800. doi: 10.1105/tpc.114.135467. PubMed DOI PMC

Yuan D., Lai J., Xu P., Zhang S., Zhang J., Li C., Wang Y., Du J., Liu Y., Yang C. AtMMS21 regulates DNA damage response and homologous recombination repair in Arabidopsis. DNA Repair. 2014;21:140–147. doi: 10.1016/j.dnarep.2014.04.006. PubMed DOI

Pecinka A., Liu C.H. Drugs for plant chromosome and chromatin research. Cytogenet. Genome Res. 2014;143:51–59. doi: 10.1159/000360774. PubMed DOI

Baubec T., Finke A., Mittelsten Scheid O., Pecinka A. Meristem-specific expression of epigenetic regulators safeguards transposon silencing in Arabidopsis. EMBO Rep. 2014;15:446–452. doi: 10.1002/embr.201337915. PubMed DOI PMC

Baubec T., Pecinka A., Rozhon W., Mittelsten Scheid O. Effective, homogeneous and transient interference with cytosine methylation in plant genomic DNA by zebularine. Plant J. 2009;57:542–554. doi: 10.1111/j.1365-313X.2008.03699.x. PubMed DOI PMC

Finke A., Pecinka A. (Institute of Experimental Botany A.S. C.R., Rozvojová, Czech Republic). 2018. Unpublished work.

Outwin E.A., Irmisch A., Murray J.M., O’Connell M.J. Smc5-Smc6-dependent removal of cohesin from mitotic chromosomes. Mol. Cell. Biol. 2009;29:4363–4375. doi: 10.1128/MCB.00377-09. PubMed DOI PMC

Jeppsson K., Carlborg K.K., Nakato R., Berta D.G., Lilienthal I., Kanno T., Lindqvist A., Brink M.C., Dantuma N.P., Katou Y., et al. The chromosomal association of the Smc5/6 complex depends on cohesion and predicts the level of sister chromatid entanglement. PLoS Genet. 2014;10:e1004680. doi: 10.1371/journal.pgen.1004680. PubMed DOI PMC

Lindroos H.B., Strom L., Itoh T., Katou Y., Shirahige K., Sjogren C. Chromosomal association of the Smc5/6 complex reveals that it functions in differently regulated pathways. Mol. Cell. 2006;22:755–767. doi: 10.1016/j.molcel.2006.05.014. PubMed DOI

De Piccoli G., Cortes-Ledesma F., Ira G., Torres-Rosell J., Uhle S., Farmer S., Hwang J.Y., Machin F., Ceschia A., McAleenan A., et al. Smc5-Smc6 mediate DNA double-strand-break repair by promoting sister-chromatid recombination. Nat. Cell Biol. 2006;8:1032–1034. doi: 10.1038/ncb1466. PubMed DOI PMC

Strom L., Karlsson C., Lindroos H.B., Wedahl S., Katou Y., Shirahige K., Sjogren C. Postreplicative formation of cohesion is required for repair and induced by a single DNA break. Science. 2007;317:242–245. doi: 10.1126/science.1140649. PubMed DOI

Hanin M., Mengiste T., Bogucki A., Paszkowski J. Elevated levels of intrachromosomal homologous recombination in Arabidopsis overexpressing the MIM gene. Plant J. 2000;24:183–189. doi: 10.1046/j.1365-313x.2000.00867.x. PubMed DOI

Stephan A.K., Kliszczak M., Dodson H., Cooley C., Morrison C.G. Roles of vertebrate Smc5 in sister chromatid cohesion and homologous recombinational repair. Mol. Cell. Biol. 2011;31:1369–1381. doi: 10.1128/MCB.00786-10. PubMed DOI PMC

Cimprich K.A., Cortez D. ATR: An essential regulator of genome integrity. Nat. Rev. Mol. Cell Biol. 2008;9:616–627. doi: 10.1038/nrm2450. PubMed DOI PMC

Garcia V., Bruchet H., Camescasse D., Granier F., Bouchez D., Tissier A. AtATM is essential for meiosis and the somatic response to DNA damage in plants. Plant Cell. 2003;15:119–132. doi: 10.1105/tpc.006577. PubMed DOI PMC

Culligan K.M., Robertson C.E., Foreman J., Doerner P., Britt A.B. ATR and ATM play both distinct and additive roles in response to ionizing radiation. Plant J. 2006;48:947–961. doi: 10.1111/j.1365-313X.2006.02931.x. PubMed DOI

Roitinger E., Hofer M., Kocher T., Pichler P., Novatchkova M., Yang J., Schlogelhofer P., Mechtler K. Quantitative phosphoproteomics of the ataxia telangiectasia-mutated (ATM) and ataxia telangiectasia-mutated and rad3-related (ATR) dependent DNA damage response in Arabidopsis thaliana. Mol. Cell. Proteom. 2015;14:556–571. doi: 10.1074/mcp.M114.040352. PubMed DOI PMC

Kilian J., Whitehead D., Horak J., Wanke D., Weinl S., Batistic O., D'Angelo C., Bornberg-Bauer E., Kudla J., Harter K. The AtGenExpress global stress expression data set: Protocols, evaluation and model data analysis of UV-B light, drought and cold stress responses. Plant J. 2007;50:347–363. doi: 10.1111/j.1365-313X.2007.03052.x. PubMed DOI

Devos K.M., Brown J.K., Bennetzen J.L. Genome size reduction through illegitimate recombination counteracts genome expansion in Arabidopsis. Genome Res. 2002;12:1075–1079. doi: 10.1101/gr.132102. PubMed DOI PMC

Ampatzidou E., Irmisch A., O'Connell M.J., Murray J.M. Smc5/6 is required for repair at collapsed replication forks. Mol. Cell. Biol. 2006;26:9387–9401. doi: 10.1128/MCB.01335-06. PubMed DOI PMC

Torres-Rosell J., Machin F., Farmer S., Jarmuz A., Eydmann T., Dalgaard J.Z., Aragon L. SMC5 and SMC6 genes are required for the segregation of repetitive chromosome regions. Nat. Cell Biol. 2005;7:412–419. doi: 10.1038/ncb1239. PubMed DOI

Hwang J.Y., Smith S., Ceschia A., Torres-Rosell J., Aragon L., Myung K. Smc5-Smc6 complex suppresses gross chromosomal rearrangements mediated by break-induced replications. DNA Repair. 2008;7:1426–1436. doi: 10.1016/j.dnarep.2008.05.006. PubMed DOI PMC

Menolfi D., Delamarre A., Lengronne A., Pasero P., Branzei D. Essential roles of the Smc5/6 complex in replication through natural pausing sites and endogenous DNA damage tolerance. Mol. Cell. 2015;60:835–846. doi: 10.1016/j.molcel.2015.10.023. PubMed DOI PMC

Chiolo I., Minoda A., Colmenares S.U., Polyzos A., Costes S.V., Karpen G.H. Double-strand breaks in heterochromatin move outside of a dynamic HP1a domain to complete recombinational repair. Cell. 2011;144:732–744. doi: 10.1016/j.cell.2011.02.012. PubMed DOI PMC

Ryu T., Spatola B., Delabaere L., Bowlin K., Hopp H., Kunitake R., Karpen G.H., Chiolo I. Heterochromatic breaks move to the nuclear periphery to continue recombinational repair. Nat. Cell Biol. 2015;17:1401–1411. doi: 10.1038/ncb3258. PubMed DOI PMC

Torres-Rosell J., Sunjevaric I., De Piccoli G., Sacher M., Eckert-Boulet N., Reid R., Jentsch S., Rothstein R., Aragon L., Lisby M. The Smc5-Smc6 complex and SUMO modification of Rad52 regulates recombinational repair at the ribosomal gene locus. Nat. Cell Biol. 2007;9:923–931. doi: 10.1038/ncb1619. PubMed DOI

Kozak J., West C.E., White C., da Costa-Nunes J.A., Angelis K.J. Rapid repair of DNA double strand breaks in Arabidopsis thaliana is dependent on proteins involved in chromosome structure maintenance. DNA Repair. 2009;8:413–419. doi: 10.1016/j.dnarep.2008.11.012. PubMed DOI

Branzei D., Sollier J., Liberi G., Zhao X., Maeda D., Seki M., Enomoto T., Ohta K., Foiani M. Ubc9- and mms21-mediated sumoylation counteracts recombinogenic events at damaged replication forks. Cell. 2006;127:509–522. doi: 10.1016/j.cell.2006.08.050. PubMed DOI

DiNardo S., Voelkel K., Sternglanz R. DNA topoisomerase II mutant of Saccharomyces cerevisiae: Topoisomerase II is required for segregation of daughter molecules at the termination of DNA replication. Proc. Natl. Acad. Sci. USA. 1984;81:2616–2620. doi: 10.1073/pnas.81.9.2616. PubMed DOI PMC

Bermejo R., Doksani Y., Capra T., Katou Y.M., Tanaka H., Shirahige K., Foiani M. Top1- and Top2-mediated topological transitions at replication forks ensure fork progression and stability and prevent DNA damage checkpoint activation. Genes Dev. 2007;21:1921–1936. doi: 10.1101/gad.432107. PubMed DOI PMC

Kegel A., Betts-Lindroos H., Kanno T., Jeppsson K., Strom L., Katou Y., Itoh T., Shirahige K., Sjogren C. Chromosome length influences replication-induced topological stress. Nature. 2011;471:392–396. doi: 10.1038/nature09791. PubMed DOI

Gallego-Paez L.M., Tanaka H., Bando M., Takahashi M., Nozaki N., Nakato R., Shirahige K., Hirota T. Smc5/6-mediated regulation of replication progression contributes to chromosome assembly during mitosis in human cells. Mol. Biol. Cell. 2014;25:302–317. doi: 10.1091/mbc.E13-01-0020. PubMed DOI PMC

Cohen-Fix O. The making and breaking of sister chromatid cohesion. Cell. 2001;106:137–140. doi: 10.1016/S0092-8674(01)00439-1. PubMed DOI

Schubert V., Klatte M., Pecinka A., Meister A., Jasencakova Z., Schubert I. Sister chromatids are often incompletely aligned in meristematic and endopolyploid interphase nuclei of Arabidopsis thaliana. Genetics. 2006;172:467–475. doi: 10.1534/genetics.105.048363. PubMed DOI PMC

Bermudez-Lopez M., Ceschia A., de Piccoli G., Colomina N., Pasero P., Aragon L., Torres-Rosell J. The Smc5/6 complex is required for dissolution of DNA-mediated sister chromatid linkages. Nucleic Acids Res. 2010;38:6502–6512. doi: 10.1093/nar/gkq546. PubMed DOI PMC

Bermudez-Lopez M., Villoria M.T., Esteras M., Jarmuz A., Torres-Rosell J., Clemente-Blanco A., Aragon L. Sgs1’s roles in DNA end resection, HJ dissolution, and crossover suppression require a two-step SUMO regulation dependent on Smc5/6. Genes Dev. 2016;30:1339–1356. doi: 10.1101/gad.278275.116. PubMed DOI PMC

Bonner J.N., Choi K., Xue X., Torres N.P., Szakal B., Wei L., Wan B., Arter M., Matos J., Sung P., et al. Smc5/6 mediated sumoylation of the Sgs1-Top3-Rmi1 complex promotes removal of recombination intermediates. Cell Rep. 2016;16:368–378. doi: 10.1016/j.celrep.2016.06.015. PubMed DOI PMC

Bermudez-Lopez M., Aragon L. Smc5/6 complex regulates Sgs1 recombination functions. Curr. Genet. 2017;63:381–388. doi: 10.1007/s00294-016-0648-5. PubMed DOI PMC

Choi K., Szakal B., Chen Y.H., Branzei D., Zhao X. The Smc5/6 complex and Esc2 influence multiple replication-associated recombination processes in Saccharomyces cerevisiae. Mol. Biol. Cell. 2010;21:2306–2314. doi: 10.1091/mbc.E10-01-0050. PubMed DOI PMC

Chen Y.H., Choi K., Szakal B., Arenz J., Duan X., Ye H., Branzei D., Zhao X. Interplay between the Smc5/6 complex and the Mph1 helicase in recombinational repair. Proc. Natl. Acad. Sci. USA. 2009;106:21252–21257. doi: 10.1073/pnas.0908258106. PubMed DOI PMC

Schmid M., Davison T.S., Henz S.R., Pape U.J., Demar M., Vingron M., Scholkopf B., Weigel D., Lohmann J.U. A gene expression map of Arabidopsis thaliana development. Nat. Genet. 2005;37:501–506. doi: 10.1038/ng1543. PubMed DOI

Song J., Durrant W.E., Wang S., Yan S., Tan E.H., Dong X. DNA repair proteins are directly involved in regulation of gene expression during plant immune response. Cell Host Microbe. 2011;9:115–124. doi: 10.1016/j.chom.2011.01.011. PubMed DOI

Ishida T., Yoshimura M., Miura K., Sugimoto K. MMS21/HPY2 and SIZ1, two Arabidopsis SUMO E3 ligases, have distinct functions in development. PLoS ONE. 2012;7:e46897. doi: 10.1371/journal.pone.0046897. PubMed DOI PMC

Kwak J.S., Son G.H., Kim S.I., Song J.T., Seo H.S. Arabidopsis HIGH PLOIDY2 Sumoylates and Stabilizes Flowering Locus C through Its E3 Ligase Activity. Front. Plant Sci. 2016;7:530. doi: 10.3389/fpls.2016.00530. PubMed DOI PMC

Liu M., Shi S.F., Zhang S.C., Xu P.L., Lai J.B., Liu Y.Y., Yuan D.K., Wang Y.Q., Du J.J., Yang C.W. SUMO E3 ligase AtMMS21 is required for normal meiosis and gametophyte development in Arabidopsis. BMC Plant. Biol. 2014;14 doi: 10.1186/1471-2229-14-153. PubMed DOI PMC

Kimura S., Sakaguchi K. DNA repair in plants. Chem. Rev. 2006;106:753–766. doi: 10.1021/cr040482n. PubMed DOI

Yadav R.K., Girke T., Pasala S., Xie M., Reddy G.V. Gene expression map of the Arabidopsis shoot apical meristem stem cell niche. Proc. Natl. Acad. Sci. USA. 2009;106:4941–4946. doi: 10.1073/pnas.0900843106. PubMed DOI PMC

Diaz M., Pecinka A. Seeds as emerging hotspot for maintenance of genome stability. Cytol. Focus. 2017;82:467–470. doi: 10.1508/cytologia.82.467. DOI

Liu Y., Lai J., Yu M., Wang F., Zhang J., Jiang J., Hu H., Wu Q., Lu G., Xu P., et al. The Arabidopsis SUMO E3 ligase AtMMS21 dissociates the E2Fa/DPa complex in cell cycle regulation. Plant Cell. 2016 doi: 10.1105/tpc.16.00439. PubMed DOI PMC

Zhang J., Lai J., Wang F., Yang S., He Z., Jiang J., Li Q., Wu Q., Liu Y., Yu M., et al. A SUMO Ligase AtMMS21 Regulates the Stability of the Chromatin Remodeler BRAHMA in Root Development. Plant Physiol. 2017;173:1574–1582. doi: 10.1104/pp.17.00014. PubMed DOI PMC

Andres F., Coupland G. The genetic basis of flowering responses to seasonal cues. Nat. Rev. Genet. 2012;13:627–639. doi: 10.1038/nrg3291. PubMed DOI

Mylne J.S., Barrett L., Tessadori F., Mesnage S., Johnson L., Bernatavichute Y.V., Jacobsen S.E., Fransz P., Dean C. LHP1, the Arabidopsis homologue of HETEROCHROMATIN PROTEIN1, is required for epigenetic silencing of FLC. Proc. Natl. Acad. Sci. USA. 2006;103:5012–5017. doi: 10.1073/pnas.0507427103. PubMed DOI PMC

Bastow R., Mylne J.S., Lister C., Lippman Z., Martienssen R.A., Dean C. Vernalization requires epigenetic silencing of FLC by histone methylation. Nature. 2004;427:164–167. doi: 10.1038/nature02269. PubMed DOI

Schubert D., Primavesi L., Bishopp A., Roberts G., Doonan J., Jenuwein T., Goodrich J. Silencing by plant Polycomb-group genes requires dispersed trimethylation of histone H3 at lysine 27. EMBO J. 2006;25:4638–4649. doi: 10.1038/sj.emboj.7601311. PubMed DOI PMC

Tanksley S.D., McCouch S.R. Seed banks and molecular maps: Unlocking genetic potential from the wild. Science. 1997;277:1063–1066. doi: 10.1126/science.277.5329.1063. PubMed DOI

Bewley J.D. Seed Germination and Dormancy. Plant Cell. 1997;9:1055–1066. doi: 10.1105/tpc.9.7.1055. PubMed DOI PMC

McElver J., Tzafrir I., Aux G., Rogers R., Ashby C., Smith K., Thomas C., Schetter A., Zhou Q., Cushman M.A., et al. Insertional mutagenesis of genes required for seed development in Arabidopsis thaliana. Genetics. 2001;159:1751–1763. PubMed PMC

Liu C.M., McElver J., Tzafrir I., Joosen R., Wittich P., Patton D., Van Lammeren A.A., Meinke D. Condensin and cohesin knockouts in Arabidopsis exhibit a titan seed phenotype. Plant J. 2002;29:405–415. doi: 10.1046/j.1365-313x.2002.01224.x. PubMed DOI

Tzafrir I., McElver J.A., Liu Cm C.M., Yang L.J., Wu J.Q., Martinez A., Patton D.A., Meinke D.W. Diversity of TITAN functions in Arabidopsis seed development. Plant Physiol. 2002;128:38–51. doi: 10.1104/pp.010911. PubMed DOI PMC

Zhang S., Qi Y., Liu M., Yang C. SUMO E3 ligase AtMMS21 regulates drought tolerance in Arabidopsis thaliana(F) J. Integr. Plant Biol. 2013;55:83–95. doi: 10.1111/jipb.12024. PubMed DOI

Cao H., Glazebrook J., Clarke J.D., Volko S., Dong X. The Arabidopsis NPR1 gene that controls systemic acquired resistance encodes a novel protein containing ankyrin repeats. Cell. 1997;88:57–63. doi: 10.1016/S0092-8674(00)81858-9. PubMed DOI

Ryals J., Weymann K., Lawton K., Friedrich L., Ellis D., Steiner H.Y., Johnson J., Delaney T.P., Jesse T., Vos P., et al. The Arabidopsis NIM1 protein shows homology to the mammalian transcription factor inhibitor I kappa B. Plant Cell. 1997;9:425–439. doi: 10.1105/tpc.9.3.425. PubMed DOI PMC

Li X., Zhang Y., Clarke J.D., Li Y., Dong X. Identification and cloning of a negative regulator of systemic acquired resistance, SNI1, through a screen for suppressors of npr1-1. Cell. 1999;98:329–339. doi: 10.1016/S0092-8674(00)81962-5. PubMed DOI

Durrant W.E., Wang S., Dong X.N. Arabidopsis SNI1 and RAD51D regulate both gene transcription and DNA recombination during the defense response. Proc. Natl. Acad. Sci. USA. 2007;104:4223–4227. doi: 10.1073/pnas.0609357104. PubMed DOI PMC

Wang S., Durrant W.E., Song J., Spivey N.W., Dong X. Arabidopsis BRCA2 and RAD51 proteins are specifically involved in defense gene transcription during plant immune responses. Proc. Natl. Acad. Sci. USA. 2010;107:22716–22721. doi: 10.1073/pnas.1005978107. PubMed DOI PMC

Decorsiere A., Mueller H., van Breugel P.C., Abdul F., Gerossier L., Beran R.K., Livingston C.M., Niu C., Fletcher S.P., Hantz O., et al. Hepatitis B virus X protein identifies the Smc5/6 complex as a host restriction factor. Nature. 2016;531:386–389. doi: 10.1038/nature17170. PubMed DOI

Laflamme G., Tremblay-Boudreault T., Roy M.A., Andersen P., Bonneil E., Atchia K., Thibault P., D'Amours D., Kwok B.H. Structural maintenance of chromosome (SMC) proteins link microtubule stability to genome integrity. J. Biol. Chem. 2014;289:27418–27431. doi: 10.1074/jbc.M114.569608. PubMed DOI PMC

SMC5/6 complex-mediated SUMOylation stimulates DNA-protein cross-link repair in Arabidopsis

Multiple Roles of SMC5/6 Complex during Plant Sexual Reproduction

Defects in meiotic chromosome segregation lead to unreduced male gametes in Arabidopsis SMC5/6 complex mutants

The SMC5/6 Complex Subunit NSE4A Is Involved in DNA Damage Repair and Seed Development

Arabidopsis NSE4 Proteins Act in Somatic Nuclei and Meiosis to Ensure Plant Viability and Fertility

SMC5/6: Multifunctional Player in Replication