Abstract
Transformation-associated recombination (TAR) cloning represents a unique tool for isolation and manipulation of large DNA molecules. The technique exploits a high level of homologous recombination in the yeast Sacharomyces cerevisiae. So far, TAR cloning is the only method available to selectively recover chromosomal segments up to 300 kb in length from complex and simple genomes. In addition, TAR cloning allows the assembly and cloning of entire microbe genomes up to several Mb as well as engineering of large metabolic pathways. In this review, we summarize applications of TAR cloning for functional/structural genomics and synthetic biology.
This is a preview of subscription content, access via your institution.





References
Agarwal V, El Gamal AA, Yamanaka K, Poth D, Kersten RD, Schorn M, Allen EE, Moore BS (2014) Biosynthesis of polybrominated aromatic organic compounds by marine bacteria. Nat Chem Biol 10:640–U182
Ando H, Lemire S, Pires DP, Lu TK (2015) Engineering modular viral scaffolds for targeted bacterial population editing. Cell Syst 1:187–196
Annab L, Kouprina N, Solomon G, Cable L, Hill D, Barrett JC, Larionov V, Afshari C (2000) Isolation of functional copy of the human BRCA1 gene by TAR cloning in yeast. Gene 250:201–208
Annaluru N, Muller H, La M, Ramalingam S, Stracquadanio G, Richardson SM, Dymond JS, Kuang Z, Scheifele LZ, Cooper EM, Cai Y, Zeller K, Agmon N, Han JS, Hadjithomas M, Tullman J, Caravelli K, Cirelli K, Guo Z, London V, Yeluru A, Murugan S, Kandavelou K, Agier N, Fischer G, Yang K, Martin JA, Bilgel M, Bohutski P, Boulier KM, Capaldo BJ, Chang J, Charoen K, Choi WJ, Deng P, DiCarlo JE, Doong J, Dunn J, Feinberg JI, Fernandez C, Floria CE, Gladowski D, Hadidi P, Ishizuka I, Jabbari J, Lau CY, Lee PA, Li S, Lin D, Linder ME, Ling J, Liu J, Liu J, London M, Ma H, Mao J, McDade JE, McMillan A, Moore AM, Oh WC, Ouyang Y, Patel R, Paul M, Paulsen LC, Qiu J, Rhee A, Rubashkin MG, Soh IY, Sotuyo NE, Srinivas V, Suarez A, Wong A, Wong R, Xie WR, Xu Y, Yu AT, Koszul R, Bader JS, Boeke JD, Chandrasegaran S (2014) Total synthesis of a functional designer eukaryotic chromosome. Science 344:55–58
Asakawa S, Abe I, Kudoh Y, Kishi N, Wang Y, Kubota R, Kudoh J, Kawasaki K, Minoshima S, Shimizu N (1997) Human BAC library: construction and rapid screening. Gene 191:69–79
Becker M, Aitcheson N, Byles E, Wickstead B, Louis E, Rudenko G (2004) Isolation of the repertoire of VSG expression site containing telomeres of Trypanosoma brucei 427 using transformation-associated recombination in yeast. Genome Res 14:2319–2329
Benders GA, Noskov VN, Denisova EA, Lartigue C, Gibson DG, Assad-Garcia N, Chuang RY, Carrera W, Moodie M, Algire MA, Phan Q, Alperovich N, Vashee S, Merryman C, Venter JC, Smith HO, Glass JI, Hutchison CA 3rd (2010) Cloning whole bacterial genomes in yeast. Nucleic Acids Res 38:2558–2569
Bergmann JH, Martins NM, Larionov V, Masumoto H, Earnshaw WC (2012) HACking the centromere chromatin code: insights from human artificial chromosomes. Chromosome Res 20:505–519
Bonet B, Teufel R, Crüsemann M, Ziemert N, Moore BS (2015) Direct capture and heterologous expression of Salinispora natural product genes for the biosynthesis of enterocin. J Nat Prod 78:539–542
Brochado AR, Patil KR (2013) Overexpression of O-methyltransferase leads to improved vanillin production in baker’s yeast only when complemented with model-guided network engineering. Biotechnol Bioeng 110:656–659
Buchholz CJ, Mühlebach MD, Cichutek K (2009) Lentiviral vectors with measles virus glycoproteins—dream team for gene transfer? Trends Biotechnol 27:259–265
Cano-Prieto C, García-Salcedo R, Sánchez-Hidalgo M, Braña AF, Fiedler HP, Méndez C, Salas JA, Olano C (2015) Genome mining of streptomyces sp. Tü 6176: characterization of the nataxazole biosynthesis pathway. Chembiochem 16:1461–1473
Ebersole TA, Ross A, Clark E, McGill N, Schindelhauer D, Cooke H, Grimes B (2000) Mammalian artificial chromosome formation from circular alphoid input DNA does not require telomere repeats. Hum Mol Genet 9:1623–1631
Ebersole T, Okamoto Y, Noskov VN, Kouprina N, Kim JH, Leem SH, Barrett JC, Masumoto H, Larionov V (2005) Rapid generation of long synthetic tandem repeats and its application for analysis in human artificial chromosome formation. Nucleic Acids Res 33, e130
Epstein AL (2009) Progress and prospects: biological properties and technological advances of herpes simplex virus type 1-based amplicon vectors. Gene Ther 16:709–715
Feng Z, Kallifidas D, Brady SF (2011) Functional analysis of environmental DNA-derived type II polyketide synthases reveals structurally diverse secondary metabolites. Proc Natl Acad Sci U S A 108:12629–12634
Gaida A, Becker MM, Schmid CD, Bühlmann T, Louis EJ, Beck HP (2011) Cloning of the repertoire of individual Plasmodium falciparum var genes using transformation associated recombination (TAR). PLoS One 6, e17782
Gibson DG (2014) Programming biological operating systems: genome design, assembly and activation. Nat Methods 11:521–526
Gibson DG, Benders GA, Andrews-Pfannkoch C, Denisova EA, Baden-Tillson H, Zaveri J, Stockwell TB, Brownley A, Thomas DW, Algire MA, Merryman C, Young L, Noskov VN, Glass JI, Venter JC, Hutchison CA 3rd, Smith HO (2008a) Complete chemical synthesis, assembly, and cloning of a Mycoplasma genitalium genome. Science 319:1215–1220
Gibson DG, Benders GA, Axelrod KC, Zaveri J, Algire MA, Moodie M, Montague MG, Venter JC, Smith HO, Hutchison CA 3rd (2008b) One-step assembly in yeast of 25 overlapping DNA fragments to form a complete synthetic Mycoplasma genitalium genome. Proc Natl Acad Sci U S A 105:20404–20409
Gibson DG, Glass JI, Lartigue C, Noskov VN, Chuang RY, Algire MA, Benders GA, Montague MG, Ma L, Moodie MM, Merryman C, Vashee S, Krishnakumar R, Assad-Garcia N, Andrews-Pfannkoch C, Denisova EA, Young L, Qi ZQ, Segall-Shapiro TH, Calvey CH, Parmar PP, Hutchison CA 3rd, Smith HO, Venter JC (2010) Creation of a bacterial cell controlled by a chemically synthesized genome. Science 329:52–56
Giordano D, Coppola D, Russo R, Denaro R, Giuliano L, Lauro FM, di Prisco G, Verde C (2015) Marine microbial secondary metabolites: pathways, evolution and physiological. Adv Microb Physiol 66:357–428
Grimwood J, Gordon LA, Olsen A, Terry A, Schmutz J, Lamerdin J, Hellsten U, Goodstein D, Couronne O, Tran-Gyamfi M, Aerts A, Altherr M, Ashworth L, Bajorek E, Black S, Branscomb E, Caenepeel S, Carrano A, Caoile C, Chan YM, Christensen M, Cleland CA, Copeland A, Dalin E, Dehal P, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Garcia C, Georgescu AM, Glavina T, Gomez M, Gonzales E, Groza M, Hammon N, Hawkins T, Haydu L, Ho I, Huang W, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Larionov V, Leem SH, Lopez F, Lou Y, Lowry S, Malfatti S, Martinez D, McCready P, Medina C, Morgan J, Nelson K, Nolan M, Ovcharenko I, Pitluck S, Pollard M, Popkie AP, Predki P, Quan G, Ramirez L, Rash S, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, She X, Smith D, Slezak T, Solovyev V, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wagner M, Wheeler J, Wu K, Xie G, Yang J, Dubchak I, Furey TS, DeJong P, Dickson M, Gordon D, Eichler EE, Pennacchio LA, Richardson P, Stubbs L, Rokhsar DS, Myers RM, Rubin EM, Lucas SM (2004) The DNA sequence and biology of human chromosome 19. Nature 428:529–535
Harrington JJ, Van Bokkelen G, Mays RW, Gustashaw K, Willard HF (1997) Formation of de novo centromeres and construction of first-generation human artificial microchromosomes. Nat Genet 15:345–355
Henning KA, Novotny EA, Compton ST, Guan XY, Liu PP, Ashlock MA (1999) Human artificial chromosomes generated by modification of a yeast artificial chromosome containing both human alpha satellite and single-copy DNA sequences. Proc Natl Acad Sci U S A 96:592–597
Hinnen A, Hicks JB, Fink GR (1978) Transformation of yeast. Proc Natl Acad Sci U S A 75:1929–1933
Horikawa I, Chiang JC, Patterson T, Feigenbaum L, Leem SH, Michishita E, Larionov V, Hodes RJ, Barrett JC (2005) Differential cis-regulation of human versus mouse TERT gene expression in vivo: identification of a human-specific repression element. Proc Natl Acad Sci U S A 102:18437–18442
Ikeno M, Grimes B, Okazaki T, Nakano M, Saitoh K, Hoshino H, McGill NI, Cooke H, Masumoto H (1998) Construction of YAC-based mammalian artificial chromosomes. Nat Biotechnol 16:431–439
Ikeno M, Inagaki H, Nagata K, Morita M, Ichinose H, Okazaki T (2002) Generation of human artificial chromosomes expressing naturally controlled guanosine triphosphate cyclohydrolase I gene. Genes Cells 7:1021–1032
Karas BJ, Tagwerker C, Yonemoto IT, Hutchison CA 3rd, Smith HO (2012) Cloning the Acholeplasma laidlawii PG-8A genome in Saccharomyces cerevisiae as a yeast centromeric plasmid. ACS Synth Biol 1:22–28
Karas BJ, Molparia B, Jablanovic J, Hermann WJ, Lin YC, Dupont CL, Tagwerker C, Yonemoto IT, Noskov VN, Chuang RY, Allen AE, Glass JI, Hutchison CA 3rd, Smith HO, Venter JC, Weyman PD (2013) Assembly of eukaryotic algal chromosomes in yeast. J Biol Eng 7:30
Karas BJ, Suzuki Y, Weyman PD (2015) Strategies for cloning and manipulating natural and synthetic chromosomes. Chromosome Res 23:57–68
Katoh M, Ayabe F, Norikane S, Okada T, Masumoto H, Horike S, Shirayoshi Y, Oshimura M (2004) Construction of a novel human artificial chromosome vector for gene delivery. Biochem Biophys Res Commun 321:280–290
Katona RL (2015) De novo formed satellite DNA-based mammalian artificial chromosomes and their possible applications. Chromosome Res 23:143–157
Kazuki Y, Oshimura M (2011) Human artificial chromosomes for gene delivery and the development of animal models. Mol Ther 19:1591–1601
Kim JH, Leem SH, Sunwoo Y, Kouprina N (2003) Separation of long-range human TERT gene haplotypes by transformation-associated recombination cloning in yeast. Oncogene 22:2443–2456
Kim JH, Feng Z, Bauer JD, Kallifidas D, Calle PY, Brady SF (2010) Cloning large natural product gene clusters from the environment: piecing environmental DNA gene clusters back together with TAR. Biopolymers 93:833–844
Kim JH, Kononenko A, Erliandri I, Kim TA, Nakano M, Iida Y, Barrett JC, Oshimura M, Masumoto H, Earnshaw WC, Larionov V, Kouprina N (2011) Human artificial chromosome (HAC) vector with a conditional centromere for correction of genetic deficiencies in human cells. Proc Natl Acad Sci U S A 108:20048–20053
Kononenko AV, Bansal R, Lee NC, Grimes BR, Masumoto H, Earnshaw WC, Larionov V, Kouprina N (2014) A portable BRCA1-HAC (human artificial chromosome) module for analysis of BRCA1 tumor suppressor function. Nucleic Acids Res 42(21)
Kouprina N, Larionov V (2003) Exploiting the yeast Saccharomyces cerevisiae for the study of the organization and evolution of complex genomes. FEMS Microbiol Rev 27:629–649
Kouprina N, Larionov V (2006) TAR cloning: insights into gene function, long-range haplotypes and genome structure and evolution. Nat Rev Genet 7:805–812
Kouprina N, Larionov V (2008) Selective isolation of genomic loci from complex genomes by transformation-associated recombination cloning in the yeast Saccharomyces cerevisiae. Nat Protoc 3:371–377
Kouprina N, Annab L, Graves J, Afshari C, Barrett JC, Resnick MA, Larionov V (1998) Functional copies of a human gene can be directly isolated by TAR cloning with a small 3′ end target sequence. Proc Natl Acad Sci U S A 95:4469–4474
Kouprina N, Leem SH, Solomon G, Ly A, Koriabine M, Otstot J, Pak E, Dutra A, Zhao S, Barrett JC, Larionov V (2003a) Segments missing from the draft human genome sequence can be isolated by TAR cloning in yeast. EMBO Rep 4:257–262
Kouprina N, Ebersole T, Koriabine M, Pak E, Rogozin IB, Katoh M, Oshimura M, Ogi K, Peredelchuk M, Solomon G, Brown W, Barrett JC, Larionov V (2003b) Cloning of human centromeres by transformation-associated recombination in yeast and generation of functional human artificial chromosomes. Nucleic Acids Res 31:922–934
Kouprina N, Mullokandov M, Rogozin IB, Collins NK, Solomon G, Otstot J, Risinger JI, Koonin EV, Barrett JC, Larionov V (2004a) The SPANX gene family of cancer/testis-specific antigens: rapid evolution and amplification in African great apes and hominids. Proc Natl Acad Sci U S A 101:3077–3082
Kouprina N, Pavlicek A, Mochida GH, Solomon G, Gersch W, Yoon YH, Collura R, Ruvolo M, Barrett JC, Woods CG, Walsh CA, Jurka J, Larionov V (2004b) Accelerated evolution of the ASPM gene controlling brain size begins prior to human brain expansion. PLoS Biol 2:653–663
Kouprina N, Pavlicek A, Noskov VN, Solomon G, Otstot J, Isaacs W, Carpten JD, Trent JM, Schleutker J, Barrett JC, Jurka J, Larionov V (2005a) Dynamic structure of the SPANX gene cluster mapped to the prostate cancer susceptibility locus HPCX at Xq27. Genome Res 15:1477–1486
Kouprina N, Pavlicek A, Collins NK, Nakano M, Noskov VN, Ohzeki JI, Mochida GH, Risinger JI, Goldsmitt P, Gunsior M, Solomon G, Gersch W, Kim JH, Barrett JC, Walsh CA, Jurka J, Masumoto H, Larionov V (2005b) The microcephaly ASPM gene is expressed in proliferating tissues and encodes for a mitotic spindle protein. Hum Mol Genetics 14:2155–2165
Kouprina N, Noskov VN, Pavlicek A, Collins NK, Schoppee Bortz PD, Ottolenghi C, Loukinov D, Goldsmith P, Risinger JI, Kim JH, Westbrook VA, Solomon G, Sounders H, Herr JC, Jurka J, Lobanenkov V, Schlessinger D, Larionov V (2007a) Evolutionary diversification of SPANX-N sperm protein gene structure and expression. PLoS One 2, e359
Kouprina N, Noskov VN, Solomon G, Otstot J, Isaacs W, Xu J, Schleutker J, Larionov V (2007b) Mutational analysis of SPANX genes in families with X-linked prostate cancer. Prostate 67:820–828
Kouprina N, Lee NC, Pavlicek A, Samoshkin A, Kim JH, Lee HS, Varma S, Reinhold WC, Otstot J, Solomon G, Davis S, Meltzer PS, Schleutker J, Larionov V (2012) Exclusion of the 750-kb genetically unstable region at Xq27 as a candidate locus for prostate malignancy in HPCX1-linked families. Genes Chromosomes Cancer 51:933–948
Kouprina N, Earnshaw WC, Masumoto H, Larionov V (2013) A new generation of human artificial chromosomes for functional genomics and gene therapy. Cell Mol Life Sci 70:1135–1148
Kouprina N, Tomilin AN, Masumoto H, Earnshaw WC, Larionov V (2014) Human artificial chromosome-based gene delivery vectors for biomedicine and biotechnology. Expert Opin Drug Deliv 11:517–535
Kuleshov V, Xie D, Chen R, Pushkarev D, Ma Z, Blauwkamp T, Kertesz M, Snyder M (2014) Whole-genome haplotyping using long reads and statistical methods. Nat Biotechnol 32:261–266
Kunes S, Botstein D, Fox MS (1985) Transformation of yeast with linearized plasmid DNA. Formation of inverted dimers and recombinant plasmid products. J Mol Biol 184:375–387
Larionov V, Kouprina N, Graves J, Chen XN, Korenberg JR, Resnick MA (1996) Specific cloning of human DNA as yeast artificial chromosomes by transformation-associated recombination. Proc Natl Acad Sci U S A 93:491–496
Larionov V, Kouprina N, Solomon G, Barrett JC, Resnick MA (1997) Direct isolation of human BRCA2 gene by transformation-associated recombination in yeast. Proc Natl Acad Sci U S A 94:7384–7387
Lartigue C, Vashee S, Algire MA, Chuang RY, Benders GA, Ma L, Noskov VN, Denisova EA, Gibson DG, Assad-Garcia N, Alperovich N, Thomas DW, Merryman C, Hutchison CA 3rd, Smith HO, Venter JC, Glass JI (2009) Creating bacterial strains from genomes that have been cloned and engineered in yeast. Science 325:1693–1696
Lee NC, Larionov V, Kouprina N (2015) Highly efficient CRISPR/Cas9-mediated TAR cloning of genes and chromosomal loci from complex genomes in yeast. Nucleic Acids Res 43, e55
Leem SH, Londono-Vallejo JA, Kim JH, Bui H, Tubacher E, Solomon G, Park JE, Horikawa I, Kouprina N, Barrett JC, Larionov V (2002) Cloning of the human telomerase gene: complete genomic sequence and analysis of tandem repeats polymorphisms in intronic regions. Oncogene 21:769–777
Leem SH, Kouprina N, Grimwood J, Kim JH, Mullokandov M, Yoon YH, Chae JY, Morgan J, Lucas S, Richardson P, Detter C, Glavina T, Rubin E, Barrett JC, Larionov V (2004) Closing the gaps on human chromosome 19 revealed genes with a high density of repetitive tandemly arrayed elements. Genome Res 14:239–246
Li Y, Li Z, Yamanaka K, Xu Y, Zhang W, Vlamakis H, Kolter R, Moore BS, Qian PY (2015a) Directed natural product biosynthesis gene cluster capture and expression in the model bacterium Bacillus subtilis. Sci Rep 5:9383
Li ZR, Li Y, Lai JY, Tang J, Wang B, Lu L, Zhu G, Wu X, Xu Y, Qian PY (2015b) Critical intermediates reveal new biosynthetic events in the enigmatic colibactin pathway. Chembiochem 16:1715–1719
Liskovykh M, Ponomartsev S, Popova E, Bader M, Kouprina N, Larionov V, Alenina N, Tomilin A (2015) Stable maintenance of de novo assembled human artificial chromosomes in embryonic stem cells and their differentiated progeny in mice. Cell Cycle 14:1268–1273
Lufino MM, Edser PA, Wade-Martins R (2008) Advances in high-capacity extrachromosomal vector technology: episomal maintenance, vector delivery, and transgene expression. Mol Ther 16:1525–1538
Ma H, Kunes S, Schatz PJ, Botstein D (1987) Plasmid construction by homologous recombination in yeast. Gene 58:201–216
Maier P, von Kalle C, Laufs S (2010) Retroviral vectors for gene therapy. Future Microbiol 5:1507–1523
Mejía JE, Alazami A, Willmott A, Marschall P, Levy E, Earnshaw WC, Larin Z (2002) Efficiency of de novo centromere formation in human artificial chromosomes. Genomics 79:297–304
Mingozzi F, Katherine A, High KA (2011) Therapeutic in vivo gene transfer for genetic disease using AAV: progress and challenges. Nat Rev Genet 12:341–356
Mitchell LA, Chuang J, Agmon N, Khunsriraksakul C, Phillips NA, Cai Y, Truong DM, Veerakumar A, Wang Y, Mayorga M, Blomquist P, Sadda P, Trueheart J, Boeke JD (2015) Versatile genetic assembly system (VEGAS) to assemble pathways for expression in S. cerevisiae. Nucleic Acids Res 43:6620–6630
Mizutani K (2015) High-throughput plasmid construction using homologous recombination in yeast: its mechanisms and application to protein production for X-ray crystallography. Biosci Biotechnol Biochem 79:1–10
Moralli D, Monaco ZL (2015) Developing de novo human artificial chromosomes in embryonic stem cells using HSV-1 amplicon technology. Chromosome Res 23:105–110
Nakano M, Cardinale S, Noskov VN, Gassman R, Vagnarelli P, Kandels-Lewis S, Earnshaw WC, Larionov V, Masumoto H (2008) Inactivation of a human kinetochore by a specific targeting of chromatin modifiers. Dev Cell 14:507–522
Nihei N, Kouprina N, Larionov V, Oshima J, Martin GM, Ichikawa T, Barrett JC (2002) Functional evidence for a metastasis suppressor gene for rat prostate cancer within a 60 kb region on human chromosome 8p21-p12. Cancer Res 62:367–370
Noskov V, Koriabine M, Solomon G, Randolph M, Barrett JC, Leem SH, Stubbs L, Kouprina N, Larionov V (2001) Defining the minimal length of sequence homology required for selective gene isolation by TAR cloning. Nucleic Acids Res 29, E62
Noskov VN, Kouprina N, Leem SH, Ouspenski I, Barrett JC, Larionov V (2003a) A general cloning system to selectively isolate any eukaryotic or prokaryotic genomic region in yeast. BMC Genomics 4:16
Noskov VN, Leem SH, Solomon G, Mullokandov M, Chae JY, Yoon YH, Shin YS, Kouprina N, Larionov V (2003b) A novel strategy for analysis of gene homologues and segmental genome duplications. J Mol Evol 56:702–710
Noskov VN, Karas BJ, Young L, Chuang RY, Gibson DG, Lin YC, Stam J, Yonemoto IT, Suzuki Y, Andrews-Pfannkoch C, Glass JI, Smith HO, Hutchison CA 3rd, Venter JC, Weyman PD (2012) Assembly of large, high G+C bacterial DNA fragments in yeast. ACS Synth Biol 1:267–273
Ohzeki J, Larionov V, Earnshaw WC, Masumoto H (2015) Genetic and epigenetic regulation of centromeres: a look at HAC formation. Chromosome Res 23:87–103
Ongley SE, Bian X, Neilan BA, Müller R (2013) Recent advances in the heterologous expression of microbial natural product biosynthetic pathways. Nat Prod Rep 30:1121–1138
Orr-Weaver TL, Szostak JW, Rothstein RJ (1981) Yeast transformation: a model system for the study of recombination. Proc Natl Acad Sci U S A 78:6354–6358
Oshimura M, Uno N, Kazuki Y, Katoh M, Inoue T (2015) A pathway from chromosome transfer to engineering resulting in human and mouse artificial chromosomes for a variety of applications to bio-medical challenges. Chromosome Res 23:111–133
Pavlicek A, Noskov N, Kouprina N, Barrett JC, Jurka J, Larionov V (2004) Evolution of the tumor suppressor BRCA1 locus in primates: implications for cancer predisposition. Hum Mol Genet 13:1–15
Ross AC, Gulland LE, Dorrestein PC, Moore BS (2015) Targeted capture and heterologous expression of the Pseudoalteromonas alterochromide gene cluster in Escherichia coli represents a promising natural product exploratory platform. ACS Synth Biol 4:414–420
Salem RM, Wessel J, Schork NJ (2005) A comprehensive literature review of haplotyping software and methods for use with unrelated individuals. Hum Genomics 2:39–66
Scherer S, Davis RW (1979) Replacement of chromosomal segments with altered DNA sequences constructed in vitro. Proc Natl Acad Sci U S A 76:4951–4955
Shao Z, Zhao H, Zhao H (2009) DNA assembler, an in vivo genetic method for rapid construction of biochemical pathways. Nucleic Acids Res 37, e16
Stinchcomb DT, Thomas M, Kelly J, Selker E, Davis RW (1980) Eukaryotic DNA segments capable of autonomous replication in yeast. Proc Natl Acad Sci U S A 77:4559–4563
Suzuki T, Kazuki Y, Oshimura M, Hara T (2014) A novel system for simultaneous or sequential integration of multiple gene-loading vectors into a defined site of a human artificial chromosome. PLoS One 9(10), e110404
Tagwerker C, Dupont CL, Karas BJ, Ma L, Chuang RY, Benders GA, Ramon A, Novotny M, Montague MG, Venepally P, Brami D, Schwartz A, Andrews-Pfannkoch C, Gibson DG, Glass JI, Smith HO, Venter JC, Hutchison CA 3rd (2012) Sequence analysis of a complete 1.66 Mb Prochlorococcus marinus MED4 genome cloned in yeast. Nucleic Acids Res 40:10375–10383
Tang X, Li J, Millán-Aguiñaga N, Zhang JJ, O’Neill EC, Ugalde JA, Jensen PR, Mantovani SM, Moore BS (2015) Identification of thiotetronic acid antibiotic biosynthetic pathways by target-directed genome mining. ACS Chem Biol 10:2841–2849
Tedesco FS, Hoshiya H, D’Antona G, Gerli MF, Messina G, Antonini S, Tonlorenzi R, Benedetti S, Berghella L, Torrente Y, Kazuki Y, Bottinelli R, Oshimura M, Cossu G (2011) Stem cell-mediated transfer of a human artificial chromosome ameliorates muscular dystrophy. Sci Transl Med 3: 96ra78
Wang M, Beck CR, English AC, Meng Q, Buhay C, Han Y, Doddapaneni HV, Yu F, Boerwinkle E, Lupski JR, Muzny DM, Gibbs RA (2015) PacBio-LITS: a large-insert targeted sequencing method for characterization of human disease-associated chromosomal structural variations. BMC Genomics 16:214
Wanisch K, Yáñez-Muñoz RJ (2009) Integration-deficient lentiviral vectors: a slow coming of age. Mol Ther 17:1316–1332
Westfall PJ, Pitera DJ, Lenihan JR, Eng D, Woolard FX, Regentin R, Horning T, Tsuruta H, Melis DJ, Owens A, Fickes S, Diola D, Benjamin KR, Keasling JD, Leavell MD, McPhee DJ, Renninger NS, Newman JD, Paddon CJ (2012) Production of amorphadiene in yeast, and its conversion to dihydroartemisinic acid, precursor to the antimalarial agent artemisinin. Proc Natl Acad Sci U S A 109:E111–E118
Yamanaka K, Reynolds KA, Kersten RD, Ryan KS, Gonzalez DJ, Nizet V, Dorrestein PC, Moore BS (2014) Direct cloning and refactoring of a silent lipopeptide biosynthetic gene cluster yields the antibiotic taromycin A. Proc Natl Acad Sci U S A 111:1957–1962
Young R, Taylor JE, Kurioka A, Becker M, Louis EJ, Rudenko G (2008) Isolation and analysis of the genetic diversity of repertoires of VSG expression site containing telomeres from Trypanosoma brucei gambiense, T. b. brucei and T. equiperdum. BMC Genomics 9:385
Yuan Y, Andersen E, Zhao H (2016) Flexible and versatile strategy for the construction of large biochemical pathways. ACS Synth Biol 5:46–52
Zhang W, Hagedorn C, Schulz E, Lipps HJ, Ehrhardt A (2014) Viral hybrid-vectors for delivery of autonomous replicons. Curr Gene Ther 14:10–23
Acknowledgments
We thank Dr. Nicolas Lee for helping in preparation of figures.
This work was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, USA (V.L. and N.K).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest. This article does not contain any studies with human participants or animals performed by any of the authors.
Additional information
This article is related to the 21st International Chromosome Conference (Foz do Iguaçu, Brazil, July 10–13, 2016).
Rights and permissions
About this article
Cite this article
Kouprina, N., Larionov, V. Transformation-associated recombination (TAR) cloning for genomics studies and synthetic biology. Chromosoma 125, 621–632 (2016). https://doi.org/10.1007/s00412-016-0588-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00412-016-0588-3
Keywords
- Transformation-associated recombination
- TAR cloning
- Human artificial chromosome
- HAC
- Synthetic biology