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<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
'''DNA topoisomerase 3-alpha''' is an [[enzyme]] that in humans is encoded by the ''TOP3A'' [[gene]].<ref name="pmid9450867">{{cite journal | vauthors = Elsea SH, Fritz E, Schoener-Scott R, Meyn MS, Patel PI | title = Gene for topoisomerase III maps within the Smith-Magenis syndrome critical region: analysis of cell-cycle distribution and radiation sensitivity | journal = American Journal of Medical Genetics | volume = 75 | issue = 1 | pages = 104–8 | date = Jan 1998 | pmid = 9450867 | pmc =  | doi = 10.1002/(SICI)1096-8628(19980106)75:1<104::AID-AJMG21>3.0.CO;2-P }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: TOP3A topoisomerase (DNA) III alpha| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7156| accessdate = }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = Topoisomerase (DNA) III alpha
| HGNCid = 11992
| Symbol = TOP3A
| AltSymbols =; TOP3
| OMIM = 601243
| ECnumber = 
| Homologene = 3394
| MGIid = 1197527
| GeneAtlas_image1 = PBB_GE_TOP3A_204946_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_TOP3A_214300_s_at_tn.png
| Function = {{GNF_GO|id=GO:0003917 |text = DNA topoisomerase type I activity}} {{GNF_GO|id=GO:0008270 |text = zinc ion binding}} {{GNF_GO|id=GO:0046872 |text = metal ion binding}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005694 |text = chromosome}}
| Process = {{GNF_GO|id=GO:0006265 |text = DNA topological change}} {{GNF_GO|id=GO:0006268 |text = DNA unwinding during replication}} {{GNF_GO|id=GO:0006304 |text = DNA modification}} {{GNF_GO|id=GO:0007001 |text = chromosome organization and biogenesis (sensu Eukaryota)}} {{GNF_GO|id=GO:0007126 |text = meiosis}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 7156
    | Hs_Ensembl = ENSG00000177302
    | Hs_RefseqProtein = NP_004609
    | Hs_RefseqmRNA = NM_004618
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 17
    | Hs_GenLoc_start = 18117960
    | Hs_GenLoc_end = 18159046
    | Hs_Uniprot = Q13472
    | Mm_EntrezGene = 21975
    | Mm_Ensembl = ENSMUSG00000002814
    | Mm_RefseqmRNA = XM_001000921
    | Mm_RefseqProtein = XP_001000921
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 11
    | Mm_GenLoc_start = 60556253
    | Mm_GenLoc_end = 60593560
    | Mm_Uniprot = Q8CDI8
  }}
}}
'''Topoisomerase (DNA) III alpha''', also known as '''TOP3A''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: TOP3A topoisomerase (DNA) III alpha| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7156| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This enzyme catalyzes the transient breaking and rejoining of a single strand of DNA which allows the strands to pass through one another, thus reducing the number of supercoils and altering the topology of DNA. This enzyme forms a complex with BLM which functions in the regulation of recombination in somatic cells.<ref name="entrez" />
{{PBB_Summary
| section_title =
| summary_text = This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This enzyme catalyzes the transient breaking and rejoining of a single strand of DNA which allows the strands to pass through one another, thus reducing the number of supercoils and altering the topology of DNA. This enzyme forms a complex with BLM which functions in the regulation of recombination in somatic cells.<ref name="entrez">{{cite web | title = Entrez Gene: TOP3A topoisomerase (DNA) III alpha| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7156| accessdate = }}</ref>
}}


==References==
== Meiosis ==
{{reflist|2}}
[[File:Homologous Recombination.jpg|thumb|400px|A current model of meiotic recombination, initiated by a double-strand break or gap, followed by pairing with an homologous chromosome and strand invasion to initiate the recombinational repair process. Repair of the gap can lead to crossover (CO) or non-crossover (NCO) of the flanking regions. CO recombination is thought to occur by the Double Holliday Junction (DHJ) model, illustrated on the right, above. NCO recombinants are thought to occur primarily by the Synthesis Dependent Strand Annealing (SDSA) model, illustrated on the left, above. Most recombination events appear to be the SDSA type.]]
==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading
| citations =
*{{cite journal  | author=Hanai R, Caron PR, Wang JC |title=Human TOP3: a single-copy gene encoding DNA topoisomerase III. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=93 |issue= 8 |pages= 3653-7 |year= 1996 |pmid= 8622991 |doi=  }}
*{{cite journal  | author=Fritz E, Elsea SH, Patel PI, Meyn MS |title=Overexpression of a truncated human topoisomerase III partially corrects multiple aspects of the ataxia-telangiectasia phenotype. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=94 |issue= 9 |pages= 4538-42 |year= 1997 |pmid= 9114025 |doi=  }}
*{{cite journal  | author=Elsea SH, Fritz E, Schoener-Scott R, ''et al.'' |title=Gene for topoisomerase III maps within the Smith-Magenis syndrome critical region: analysis of cell-cycle distribution and radiation sensitivity. |journal=Am. J. Med. Genet. |volume=75 |issue= 1 |pages= 104-8 |year= 1998 |pmid= 9450867 |doi=  }}
*{{cite journal  | author=Kim JC, Yoon JB, Koo HS, Chung IK |title=Cloning and characterization of the 5'-flanking region for the human topoisomerase III gene. |journal=J. Biol. Chem. |volume=273 |issue= 40 |pages= 26130-7 |year= 1998 |pmid= 9748294 |doi=  }}
*{{cite journal  | author=Goulaouic H, Roulon T, Flamand O, ''et al.'' |title=Purification and characterization of human DNA topoisomerase IIIalpha. |journal=Nucleic Acids Res. |volume=27 |issue= 12 |pages= 2443-50 |year= 1999 |pmid= 10352172 |doi=  }}
*{{cite journal  | author=Shimamoto A, Nishikawa K, Kitao S, Furuichi Y |title=Human RecQ5beta, a large isomer of RecQ5 DNA helicase, localizes in the nucleoplasm and interacts with topoisomerases 3alpha and 3beta. |journal=Nucleic Acids Res. |volume=28 |issue= 7 |pages= 1647-55 |year= 2000 |pmid= 10710432 |doi=  }}
*{{cite journal  | author=Wu L, Davies SL, North PS, ''et al.'' |title=The Bloom's syndrome gene product interacts with topoisomerase III. |journal=J. Biol. Chem. |volume=275 |issue= 13 |pages= 9636-44 |year= 2000 |pmid= 10734115 |doi=  }}
*{{cite journal  | author=Lin CW, Darzynkiewicz Z, Li X, ''et al.'' |title=Differential expression of human topoisomerase IIIalpha during the cell cycle progression in HL-60 leukemia cells and human peripheral blood lymphocytes. |journal=Exp. Cell Res. |volume=256 |issue= 1 |pages= 225-36 |year= 2000 |pmid= 10739669 |doi= 10.1006/excr.1999.4778 }}
*{{cite journal  | author=Brosh RM, Li JL, Kenny MK, ''et al.'' |title=Replication protein A physically interacts with the Bloom's syndrome protein and stimulates its helicase activity. |journal=J. Biol. Chem. |volume=275 |issue= 31 |pages= 23500-8 |year= 2000 |pmid= 10825162 |doi= 10.1074/jbc.M001557200 }}
*{{cite journal  | author=Lodge AJ, Anderson JJ, Ng SW, ''et al.'' |title=Expression of topoisomerase IIIalpha in normal and neoplastic tissues determined by immunohistochemistry using a novel monoclonal antibody. |journal=Br. J. Cancer |volume=83 |issue= 4 |pages= 498-505 |year= 2000 |pmid= 10945498 |doi= 10.1054/bjoc.2000.1293 }}
*{{cite journal  | author=Hu P, Beresten SF, van Brabant AJ, ''et al.'' |title=Evidence for BLM and Topoisomerase IIIalpha interaction in genomic stability. |journal=Hum. Mol. Genet. |volume=10 |issue= 12 |pages= 1287-98 |year= 2001 |pmid= 11406610 |doi=  }}
*{{cite journal  | author=Freire R, d'Adda Di Fagagna F, Wu L, ''et al.'' |title=Cleavage of the Bloom's syndrome gene product during apoptosis by caspase-3 results in an impaired interaction with topoisomerase IIIalpha. |journal=Nucleic Acids Res. |volume=29 |issue= 15 |pages= 3172-80 |year= 2001 |pmid= 11470874 |doi=  }}
*{{cite journal  | author=Bi W, Yan J, Stankiewicz P, ''et al.'' |title=Genes in a refined Smith-Magenis syndrome critical deletion interval on chromosome 17p11.2 and the syntenic region of the mouse. |journal=Genome Res. |volume=12 |issue= 5 |pages= 713-28 |year= 2002 |pmid= 11997338 |doi= 10.1101/gr.73702 }}
*{{cite journal  | author=Wang Y, Lyu YL, Wang JC |title=Dual localization of human DNA topoisomerase IIIalpha to mitochondria and nucleus. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 19 |pages= 12114-9 |year= 2002 |pmid= 12209014 |doi= 10.1073/pnas.192449499 }}
*{{cite journal  | author=Wu L, Hickson ID |title=The Bloom's syndrome helicase stimulates the activity of human topoisomerase IIIalpha. |journal=Nucleic Acids Res. |volume=30 |issue= 22 |pages= 4823-9 |year= 2002 |pmid= 12433984 |doi=  }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal  | author=Meetei AR, de Winter JP, Medhurst AL, ''et al.'' |title=A novel ubiquitin ligase is deficient in Fanconi anemia. |journal=Nat. Genet. |volume=35 |issue= 2 |pages= 165-70 |year= 2003 |pmid= 12973351 |doi= 10.1038/ng1241 }}
*{{cite journal  | author=Jiao R, Bachrati CZ, Pedrazzi G, ''et al.'' |title=Physical and functional interaction between the Bloom's syndrome gene product and the largest subunit of chromatin assembly factor 1. |journal=Mol. Cell. Biol. |volume=24 |issue= 11 |pages= 4710-9 |year= 2004 |pmid= 15143166 |doi= 10.1128/MCB.24.11.4710-4719.2004 }}
*{{cite journal  | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
*{{cite journal  | author=Yin J, Sobeck A, Xu C, ''et al.'' |title=BLAP75, an essential component of Bloom's syndrome protein complexes that maintain genome integrity. |journal=EMBO J. |volume=24 |issue= 7 |pages= 1465-76 |year= 2005 |pmid= 15775963 |doi= 10.1038/sj.emboj.7600622 }}
}}
{{refend}}


{{protein-stub}}
[[Genetic recombination|Recombination]] during [[meiosis]] is often initiated by a DNA double-strand break (DSB). During recombination, sections of DNA at the 5' ends of the break are cut away in a process called ''resection''. In the ''strand invasion'' step that follows, an overhanging 3' end of the broken DNA molecule then "invades" the DNA of an homologous chromosome that is not broken forming a displacement loop ([[D-loop]]). After strand invasion, the further sequence of events may follow either of two main pathways leading to a crossover (CO) or a non-crossover (NCO) recombinant (see [[Genetic recombination]] and see Figure).  The pathway leading to a NCO is referred to as [[Synthesis-dependent strand annealing (SDSA)]].
{{WikiDoc Sources}}
 
In the plant ''[[Arabidopsis thaliana]]'', multiple mechanisms limit meiotic COs.<ref name=Arnaud>{{cite journal | vauthors = Séguéla-Arnaud M, Crismani W, Larchevêque C, Mazel J, Froger N, Choinard S, Lemhemdi A, Macaisne N, Van Leene J, Gevaert K, De Jaeger G, Chelysheva L, Mercier R | title = Multiple mechanisms limit meiotic crossovers: TOP3α and two BLM homologs antagonize crossovers in parallel to FANCM | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 112 | issue = 15 | pages = 4713–8 | date = Apr 2015 | pmid = 25825745 | pmc = 4403193 | doi = 10.1073/pnas.1423107112 }}</ref>  During meiosis TOP3A and RECQ4A/B helicase antagonize formation of COs in parallel to FANCM helicase.<ref name=Arnaud />  Sequela-Arnaud et al.<ref name=Arnaud />  suggested that CO numbers are restricted because of the long-term costs of CO recombination, that is, the breaking up of favorable genetic combinations of alleles built up by past [[natural selection]].
 
In the budding yeast ''[[Saccharomyces cerevisiae]]'', the topoisomerase III (TOP3)-[[RMI1]] heterodimer (that catalyzes DNA single-strand passage) forms a conserved complex with [[Sgs1]] helicase (an [[Homology (biology)#Orthology|ortholog]] of the human [[Bloom syndrome protein|Bloom syndrome helicase]]). This complex promotes early formation of NCO recombinants during meiosis<ref name=Kaur>{{cite journal | vauthors = Kaur H, De Muyt A, Lichten M | title = Top3-Rmi1 DNA single-strand decatenase is integral to the formation and resolution of meiotic recombination intermediates | journal = Molecular Cell | volume = 57 | issue = 4 | pages = 583–94 | date = Feb 2015 | pmid = 25699707 | doi = 10.1016/j.molcel.2015.01.020 | pmc=4338413}}</ref>  The TOP3-RMI1 strand passage activity appears to have two important functions during meiosis.<ref name=Kaur />  First, strand passage activity is employed early in coordination with [[Sgs1]] helicase to promote proper recombination pathway choice.  Second, strand passage activity is used later, independently of Sgs1 helicase, to prevent the persistence of unresolvable strand entanglements in recombination intermediates.
 
== Interactions ==
 
TOP3A has been shown to [[Protein-protein interaction|interact]] with [[Bloom syndrome protein]].<ref name=pmid10734115>{{cite journal | vauthors = Wu L, Davies SL, North PS, Goulaouic H, Riou JF, Turley H, Gatter KC, Hickson ID | title = The Bloom's syndrome gene product interacts with topoisomerase III | journal = The Journal of Biological Chemistry | volume = 275 | issue = 13 | pages = 9636–44 | date = Mar 2000 | pmid = 10734115 | doi = 10.1074/jbc.275.13.9636 }}</ref><ref name=pmid11470874>{{cite journal | vauthors = Freire R, d'Adda Di Fagagna F, Wu L, Pedrazzi G, Stagljar I, Hickson ID, Jackson SP | title = Cleavage of the Bloom's syndrome gene product during apoptosis by caspase-3 results in an impaired interaction with topoisomerase IIIalpha | journal = Nucleic Acids Research | volume = 29 | issue = 15 | pages = 3172–80 | date = Aug 2001 | pmid = 11470874 | pmc = 55826 | doi = 10.1093/nar/29.15.3172 }}</ref><ref name=pmid11406610>{{cite journal | vauthors = Hu P, Beresten SF, van Brabant AJ, Ye TZ, Pandolfi PP, Johnson FB, Guarente L, Ellis NA | title = Evidence for BLM and Topoisomerase IIIalpha interaction in genomic stability | journal = Human Molecular Genetics | volume = 10 | issue = 12 | pages = 1287–98 | date = Jun 2001 | pmid = 11406610 | doi = 10.1093/hmg/10.12.1287 }}</ref><ref name=pmid10825162>{{cite journal | vauthors = Brosh RM, Li JL, Kenny MK, Karow JK, Cooper MP, Kureekattil RP, Hickson ID, Bohr VA | title = Replication protein A physically interacts with the Bloom's syndrome protein and stimulates its helicase activity | journal = The Journal of Biological Chemistry | volume = 275 | issue = 31 | pages = 23500–8 | date = Aug 2000 | pmid = 10825162 | doi = 10.1074/jbc.M001557200 }}</ref>
 
== References ==
{{Reflist}}
 
== Further reading ==
{{Refbegin | 2}}
* {{cite journal | vauthors = Hanai R, Caron PR, Wang JC | title = Human TOP3: a single-copy gene encoding DNA topoisomerase III | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 93 | issue = 8 | pages = 3653–7 | date = Apr 1996 | pmid = 8622991 | pmc = 39666 | doi = 10.1073/pnas.93.8.3653 }}
* {{cite journal | vauthors = Fritz E, Elsea SH, Patel PI, Meyn MS | title = Overexpression of a truncated human topoisomerase III partially corrects multiple aspects of the ataxia-telangiectasia phenotype | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 9 | pages = 4538–42 | date = Apr 1997 | pmid = 9114025 | pmc = 20758 | doi = 10.1073/pnas.94.9.4538 }}
* {{cite journal | vauthors = Kim JC, Yoon JB, Koo HS, Chung IK | title = Cloning and characterization of the 5'-flanking region for the human topoisomerase III gene | journal = The Journal of Biological Chemistry | volume = 273 | issue = 40 | pages = 26130–7 | date = Oct 1998 | pmid = 9748294 | doi = 10.1074/jbc.273.40.26130 }}
* {{cite journal | vauthors = Goulaouic H, Roulon T, Flamand O, Grondard L, Lavelle F, Riou JF | title = Purification and characterization of human DNA topoisomerase IIIalpha | journal = Nucleic Acids Research | volume = 27 | issue = 12 | pages = 2443–50 | date = Jun 1999 | pmid = 10352172 | pmc = 148446 | doi = 10.1093/nar/27.12.2443 }}
* {{cite journal | vauthors = Shimamoto A, Nishikawa K, Kitao S, Furuichi Y | title = Human RecQ5beta, a large isomer of RecQ5 DNA helicase, localizes in the nucleoplasm and interacts with topoisomerases 3alpha and 3beta | journal = Nucleic Acids Research | volume = 28 | issue = 7 | pages = 1647–55 | date = Apr 2000 | pmid = 10710432 | pmc = 102787 | doi = 10.1093/nar/28.7.1647 }}
* {{cite journal | vauthors = Wu L, Davies SL, North PS, Goulaouic H, Riou JF, Turley H, Gatter KC, Hickson ID | title = The Bloom's syndrome gene product interacts with topoisomerase III | journal = The Journal of Biological Chemistry | volume = 275 | issue = 13 | pages = 9636–44 | date = Mar 2000 | pmid = 10734115 | doi = 10.1074/jbc.275.13.9636 }}
* {{cite journal | vauthors = Lin CW, Darzynkiewicz Z, Li X, Traganos F, Bedner E, Tse-Dinh YC | title = Differential expression of human topoisomerase IIIalpha during the cell cycle progression in HL-60 leukemia cells and human peripheral blood lymphocytes | journal = Experimental Cell Research | volume = 256 | issue = 1 | pages = 225–36 | date = Apr 2000 | pmid = 10739669 | doi = 10.1006/excr.1999.4778 }}
* {{cite journal | vauthors = Brosh RM, Li JL, Kenny MK, Karow JK, Cooper MP, Kureekattil RP, Hickson ID, Bohr VA | title = Replication protein A physically interacts with the Bloom's syndrome protein and stimulates its helicase activity | journal = The Journal of Biological Chemistry | volume = 275 | issue = 31 | pages = 23500–8 | date = Aug 2000 | pmid = 10825162 | doi = 10.1074/jbc.M001557200 }}
* {{cite journal | vauthors = Lodge AJ, Anderson JJ, Ng SW, Fenwick F, Steward M, Haugk B, Horne CH, Angus B | title = Expression of topoisomerase IIIalpha in normal and neoplastic tissues determined by immunohistochemistry using a novel monoclonal antibody | journal = British Journal of Cancer | volume = 83 | issue = 4 | pages = 498–505 | date = Aug 2000 | pmid = 10945498 | pmc = 2374664 | doi = 10.1054/bjoc.2000.1293 }}
* {{cite journal | vauthors = Hu P, Beresten SF, van Brabant AJ, Ye TZ, Pandolfi PP, Johnson FB, Guarente L, Ellis NA | title = Evidence for BLM and Topoisomerase IIIalpha interaction in genomic stability | journal = Human Molecular Genetics | volume = 10 | issue = 12 | pages = 1287–98 | date = Jun 2001 | pmid = 11406610 | doi = 10.1093/hmg/10.12.1287 }}
* {{cite journal | vauthors = Freire R, d'Adda Di Fagagna F, Wu L, Pedrazzi G, Stagljar I, Hickson ID, Jackson SP | title = Cleavage of the Bloom's syndrome gene product during apoptosis by caspase-3 results in an impaired interaction with topoisomerase IIIalpha | journal = Nucleic Acids Research | volume = 29 | issue = 15 | pages = 3172–80 | date = Aug 2001 | pmid = 11470874 | pmc = 55826 | doi = 10.1093/nar/29.15.3172 }}
* {{cite journal | vauthors = Bi W, Yan J, Stankiewicz P, Park SS, Walz K, Boerkoel CF, Potocki L, Shaffer LG, Devriendt K, Nowaczyk MJ, Inoue K, Lupski JR | title = Genes in a refined Smith-Magenis syndrome critical deletion interval on chromosome 17p11.2 and the syntenic region of the mouse | journal = Genome Research | volume = 12 | issue = 5 | pages = 713–28 | date = May 2002 | pmid = 11997338 | pmc = 186594 | doi = 10.1101/gr.73702 }}
* {{cite journal | vauthors = Wang Y, Lyu YL, Wang JC | title = Dual localization of human DNA topoisomerase IIIalpha to mitochondria and nucleus | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 19 | pages = 12114–9 | date = Sep 2002 | pmid = 12209014 | pmc = 129407 | doi = 10.1073/pnas.192449499 }}
* {{cite journal | vauthors = Wu L, Hickson ID | title = The Bloom's syndrome helicase stimulates the activity of human topoisomerase IIIalpha | journal = Nucleic Acids Research | volume = 30 | issue = 22 | pages = 4823–9 | date = Nov 2002 | pmid = 12433984 | pmc = 137159 | doi = 10.1093/nar/gkf611 }}
* {{cite journal | vauthors = Meetei AR, de Winter JP, Medhurst AL, Wallisch M, Waisfisz Q, van de Vrugt HJ, Oostra AB, Yan Z, Ling C, Bishop CE, Hoatlin ME, Joenje H, Wang W | title = A novel ubiquitin ligase is deficient in Fanconi anemia | journal = Nature Genetics | volume = 35 | issue = 2 | pages = 165–70 | date = Oct 2003 | pmid = 12973351 | doi = 10.1038/ng1241 }}
* {{cite journal | vauthors = Jiao R, Bachrati CZ, Pedrazzi G, Kuster P, Petkovic M, Li JL, Egli D, Hickson ID, Stagljar I | title = Physical and functional interaction between the Bloom's syndrome gene product and the largest subunit of chromatin assembly factor 1 | journal = Molecular and Cellular Biology | volume = 24 | issue = 11 | pages = 4710–9 | date = Jun 2004 | pmid = 15143166 | pmc = 416397 | doi = 10.1128/MCB.24.11.4710-4719.2004 }}
* {{cite journal | vauthors = Yin J, Sobeck A, Xu C, Meetei AR, Hoatlin M, Li L, Wang W | title = BLAP75, an essential component of Bloom's syndrome protein complexes that maintain genome integrity | journal = The EMBO Journal | volume = 24 | issue = 7 | pages = 1465–76 | date = Apr 2005 | pmid = 15775963 | pmc = 1142546 | doi = 10.1038/sj.emboj.7600622 }}
{{Refend}}

Latest revision as of 12:09, 15 September 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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n/a

UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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View/Edit Human

DNA topoisomerase 3-alpha is an enzyme that in humans is encoded by the TOP3A gene.[1][2]

Function

This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This enzyme catalyzes the transient breaking and rejoining of a single strand of DNA which allows the strands to pass through one another, thus reducing the number of supercoils and altering the topology of DNA. This enzyme forms a complex with BLM which functions in the regulation of recombination in somatic cells.[2]

Meiosis

File:Homologous Recombination.jpg
A current model of meiotic recombination, initiated by a double-strand break or gap, followed by pairing with an homologous chromosome and strand invasion to initiate the recombinational repair process. Repair of the gap can lead to crossover (CO) or non-crossover (NCO) of the flanking regions. CO recombination is thought to occur by the Double Holliday Junction (DHJ) model, illustrated on the right, above. NCO recombinants are thought to occur primarily by the Synthesis Dependent Strand Annealing (SDSA) model, illustrated on the left, above. Most recombination events appear to be the SDSA type.

Recombination during meiosis is often initiated by a DNA double-strand break (DSB). During recombination, sections of DNA at the 5' ends of the break are cut away in a process called resection. In the strand invasion step that follows, an overhanging 3' end of the broken DNA molecule then "invades" the DNA of an homologous chromosome that is not broken forming a displacement loop (D-loop). After strand invasion, the further sequence of events may follow either of two main pathways leading to a crossover (CO) or a non-crossover (NCO) recombinant (see Genetic recombination and see Figure). The pathway leading to a NCO is referred to as Synthesis-dependent strand annealing (SDSA).

In the plant Arabidopsis thaliana, multiple mechanisms limit meiotic COs.[3] During meiosis TOP3A and RECQ4A/B helicase antagonize formation of COs in parallel to FANCM helicase.[3] Sequela-Arnaud et al.[3] suggested that CO numbers are restricted because of the long-term costs of CO recombination, that is, the breaking up of favorable genetic combinations of alleles built up by past natural selection.

In the budding yeast Saccharomyces cerevisiae, the topoisomerase III (TOP3)-RMI1 heterodimer (that catalyzes DNA single-strand passage) forms a conserved complex with Sgs1 helicase (an ortholog of the human Bloom syndrome helicase). This complex promotes early formation of NCO recombinants during meiosis[4] The TOP3-RMI1 strand passage activity appears to have two important functions during meiosis.[4] First, strand passage activity is employed early in coordination with Sgs1 helicase to promote proper recombination pathway choice. Second, strand passage activity is used later, independently of Sgs1 helicase, to prevent the persistence of unresolvable strand entanglements in recombination intermediates.

Interactions

TOP3A has been shown to interact with Bloom syndrome protein.[5][6][7][8]

References

  1. ↑ Elsea SH, Fritz E, Schoener-Scott R, Meyn MS, Patel PI (Jan 1998). "Gene for topoisomerase III maps within the Smith-Magenis syndrome critical region: analysis of cell-cycle distribution and radiation sensitivity". American Journal of Medical Genetics. 75 (1): 104–8. doi:10.1002/(SICI)1096-8628(19980106)75:1<104::AID-AJMG21>3.0.CO;2-P. PMID 9450867.
  2. ↑ 2.0 2.1 "Entrez Gene: TOP3A topoisomerase (DNA) III alpha".
  3. ↑ 3.0 3.1 3.2 Séguéla-Arnaud M, Crismani W, Larchevêque C, Mazel J, Froger N, Choinard S, Lemhemdi A, Macaisne N, Van Leene J, Gevaert K, De Jaeger G, Chelysheva L, Mercier R (Apr 2015). "Multiple mechanisms limit meiotic crossovers: TOP3α and two BLM homologs antagonize crossovers in parallel to FANCM". Proceedings of the National Academy of Sciences of the United States of America. 112 (15): 4713–8. doi:10.1073/pnas.1423107112. PMC 4403193. PMID 25825745.
  4. ↑ 4.0 4.1 Kaur H, De Muyt A, Lichten M (Feb 2015). "Top3-Rmi1 DNA single-strand decatenase is integral to the formation and resolution of meiotic recombination intermediates". Molecular Cell. 57 (4): 583–94. doi:10.1016/j.molcel.2015.01.020. PMC 4338413. PMID 25699707.
  5. ↑ Wu L, Davies SL, North PS, Goulaouic H, Riou JF, Turley H, Gatter KC, Hickson ID (Mar 2000). "The Bloom's syndrome gene product interacts with topoisomerase III". The Journal of Biological Chemistry. 275 (13): 9636–44. doi:10.1074/jbc.275.13.9636. PMID 10734115.
  6. ↑ Freire R, d'Adda Di Fagagna F, Wu L, Pedrazzi G, Stagljar I, Hickson ID, Jackson SP (Aug 2001). "Cleavage of the Bloom's syndrome gene product during apoptosis by caspase-3 results in an impaired interaction with topoisomerase IIIalpha". Nucleic Acids Research. 29 (15): 3172–80. doi:10.1093/nar/29.15.3172. PMC 55826. PMID 11470874.
  7. ↑ Hu P, Beresten SF, van Brabant AJ, Ye TZ, Pandolfi PP, Johnson FB, Guarente L, Ellis NA (Jun 2001). "Evidence for BLM and Topoisomerase IIIalpha interaction in genomic stability". Human Molecular Genetics. 10 (12): 1287–98. doi:10.1093/hmg/10.12.1287. PMID 11406610.
  8. ↑ Brosh RM, Li JL, Kenny MK, Karow JK, Cooper MP, Kureekattil RP, Hickson ID, Bohr VA (Aug 2000). "Replication protein A physically interacts with the Bloom's syndrome protein and stimulates its helicase activity". The Journal of Biological Chemistry. 275 (31): 23500–8. doi:10.1074/jbc.M001557200. PMID 10825162.

Further reading

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