4cht

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Template:STRUCTURE 4cht

Contents

Crystal structure of the human topoisomerase III alpha-RMI1 complex with bound calcium ion

Template:ABSTRACT PUBMED 24509834

Function

[TOP3A_HUMAN] Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(5'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 3'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 3'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone. Essential component of the RMI complex, a complex that plays an important role in the processing of homologous recombination intermediates to limit DNA crossover formation in cells. Has DNA decatenation activity.[1] [2] [RMI1_HUMAN] Essential component of the RMI complex, a complex that plays an important role in the processing of homologous recombination intermediates to limit DNA crossover formation in cells. Promotes TOP3A binding to double Holliday junctions (DHJ) and hence stimulates TOP3A-mediated dissolution. Required for BLM phosphorylation during mitosis. Within the BLM complex, required for BLM and TOP3A stability.[3] [4] [5]

About this Structure

4cht is a 2 chain structure. Full crystallographic information is available from OCA.

Reference

  • Bocquet N, Bizard AH, Abdulrahman W, Larsen NB, Faty M, Cavadini S, Bunker RD, Kowalczykowski SC, Cejka P, Hickson ID, Thoma NH. Structural and mechanistic insight into Holliday-junction dissolution by Topoisomerase IIIalpha and RMI1. Nat Struct Mol Biol. 2014 Feb 9. doi: 10.1038/nsmb.2775. PMID:24509834 doi:http://dx.doi.org/10.1038/nsmb.2775
  1. ↑ Hanai R, Caron PR, Wang JC. Human TOP3: a single-copy gene encoding DNA topoisomerase III. Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3653-7. PMID:8622991
  2. ↑ Yang J, Bachrati CZ, Ou J, Hickson ID, Brown GW. Human topoisomerase IIIalpha is a single-stranded DNA decatenase that is stimulated by BLM and RMI1. J Biol Chem. 2010 Jul 9;285(28):21426-36. doi: 10.1074/jbc.M110.123216. Epub 2010, May 5. PMID:20445207 doi:http://dx.doi.org/10.1074/jbc.M110.123216
  3. ↑ Yin J, Sobeck A, Xu C, Meetei AR, Hoatlin M, Li L, Wang W. BLAP75, an essential component of Bloom's syndrome protein complexes that maintain genome integrity. EMBO J. 2005 Apr 6;24(7):1465-76. Epub 2005 Mar 17. PMID:15775963 doi:http://dx.doi.org/7600622
  4. ↑ Raynard S, Bussen W, Sung P. A double Holliday junction dissolvasome comprising BLM, topoisomerase IIIalpha, and BLAP75. J Biol Chem. 2006 May 19;281(20):13861-4. Epub 2006 Apr 4. PMID:16595695 doi:http://dx.doi.org/C600051200
  5. ↑ Wu L, Bachrati CZ, Ou J, Xu C, Yin J, Chang M, Wang W, Li L, Brown GW, Hickson ID. BLAP75/RMI1 promotes the BLM-dependent dissolution of homologous recombination intermediates. Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):4068-73. Epub 2006 Mar 6. PMID:16537486 doi:http://dx.doi.org/10.1073/pnas.0508295103

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