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TitleSupercoiled DNA recognition and cleavage control in topoisomerase VI.
Journal, issue, pagesNat Commun, Year 2026
Publish dateFeb 16, 2026
AuthorsDaniel E Richman / Timothy J Wendorff / Fahad Rashid / Curtis Beck / Qianyun Yan / Haley R Johnson / Ryan A Eckerty / Jonathan M Fogg / Matthew L Baker / Lynn Zechiedrich / James M Berger /
PubMed AbstractType II topoisomerases modulate DNA supercoiling and resolve chromosome entanglements. Type IIB topoisomerases, exemplified by DNA topoisomerase VI (Top6), are used by plants and archaea to support ...Type II topoisomerases modulate DNA supercoiling and resolve chromosome entanglements. Type IIB topoisomerases, exemplified by DNA topoisomerase VI (Top6), are used by plants and archaea to support endoreduplication and cell proliferation, respectively; homologs of Top6 further serve to initiate meiotic recombination in eukaryotes and constitute the nuclease portion of MksBEFG/Wadjet/Gabija bacterial defense systems. To understand how such factors act upon DNA, we determine structures of Top6 bound to supercoiled minicircles in cleaved and uncleaved states using single-particle electron cryo-microscopy. The structures show that Top6 binds a curved 74 bp region of the supercoiled minicircle DNA and that it cuts at a distinct deformability motif, explaining its preference for supercoiled substrates and highlighting the role of DNA plasticity in cleavage site selection. Dynamic protein-DNA interactions and an unanticipated tension sensor help recognize bent DNA and couple ATPase disposition to cleavage state activation. Our observations explain how DNA recognition and cleavage by type II topoisomerases are regulated by interdependent structural changes in DNA and the enzyme.
External linksNat Commun / PubMed:41698922
MethodsEM (single particle)
Resolution2.5 - 4.0 Å
Structure data

49972

9o0g

EMDB-49972, PDB-9o0g:
CryoEM structure of M. mazei topoisomerase VI(A-E342Q)-minicircle DNA complex in cleavage state
Method: EM (single particle) / Resolution: 2.5 Å

70206

9o7o

EMDB-70206, PDB-9o7o:
CryoEM structure of M. mazei topoisomerase VI(A-E342Q)-minicircle DNA complex in asymmetric state
Method: EM (single particle) / Resolution: 2.7 Å

70232

9o8p

EMDB-70232, PDB-9o8p:
CryoEM structure of M. mazei topoisomerase VI-minicircle DNA complex
Method: EM (single particle) / Resolution: 3.6 Å

70239

9o8z

EMDB-70239, PDB-9o8z:
CryoEM structure of M. mazei topoisomerase VI-minicircle DNA complex in partially unfolded transducer state
Method: EM (single particle) / Resolution: 4.0 Å

70259

9o9m

EMDB-70259, PDB-9o9m:
CryoEM structure of M. mazei topoisomerase VI-minicircle DNA complex in asymmetric state
Method: EM (single particle) / Resolution: 3.8 Å

Chemicals

ChemComp-CA:
Unknown entry

ChemComp-ANP:
PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / AMP-PNP, energy-carrying molecule analogue*YM

ChemComp-K:
Unknown entry

ChemComp-MG:
Unknown entry

Source
  • methanosarcina mazei go1 (archaea)
  • unidentified (others)
KeywordsISOMERASE/DNA / TOPRIM / GHKL / minicircle DNA / Spo11 / ISOMERASE-DNA complex

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