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Molecular mechanism of double Holliday junction dissolution.

Swuec P, Costa A - Cell Biosci (2014)

Bottom Line: Decatenation of double Holliday junctions, for example, is catalysed by two enzymes that work in tight coordination and belong to the same 'dissolvasome' complex.Within the dissolvasome, the RecQ-like BLM helicase provides the translocase function for Holliday junction migration, while the topoisomerase III alpha-RMI1 subcomplex works as a proficient DNA decatenase, together resulting in double-Holliday-junction unlinking.Here, we review the available architectural and biochemical knowledge on the dissolvasome machinery, with a focus on the structural interplay between its components.

View Article: PubMed Central - HTML - PubMed

Affiliation: Clare Hall laboratories, Cancer Research U.K. London Research Institute, London EN6 3LD, UK.

ABSTRACT
Processing of homologous recombination intermediates is tightly coordinated to ensure that chromosomal integrity is maintained and tumorigenesis avoided. Decatenation of double Holliday junctions, for example, is catalysed by two enzymes that work in tight coordination and belong to the same 'dissolvasome' complex. Within the dissolvasome, the RecQ-like BLM helicase provides the translocase function for Holliday junction migration, while the topoisomerase III alpha-RMI1 subcomplex works as a proficient DNA decatenase, together resulting in double-Holliday-junction unlinking. Here, we review the available architectural and biochemical knowledge on the dissolvasome machinery, with a focus on the structural interplay between its components.

No MeSH data available.


Related in: MedlinePlus

Topoisomerase IIIα and RMI1 reconstitute a DNA decatenase. (A) Structure of the E. coli TopoI relaxase (PDB ID 1ECL) and the E. coli TopoIII decatenase (PDB ID 1D6M). TopoIII contains specific insertions lining the pore of the topoisomerase toroid which are critical for efficient decatenation. (B) Linear and three dimensional structure of RMI1 and RMI2 (PDB IDs 3NBI and 4DAY). The decatenation loop of RMI1 is highlighted in red. (C) The N-terminal domain of RMI1 contributes to TopoIIIα a decatenation loop in trans (marked in red, PDB ID 4CGY).
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Figure 2: Topoisomerase IIIα and RMI1 reconstitute a DNA decatenase. (A) Structure of the E. coli TopoI relaxase (PDB ID 1ECL) and the E. coli TopoIII decatenase (PDB ID 1D6M). TopoIII contains specific insertions lining the pore of the topoisomerase toroid which are critical for efficient decatenation. (B) Linear and three dimensional structure of RMI1 and RMI2 (PDB IDs 3NBI and 4DAY). The decatenation loop of RMI1 is highlighted in red. (C) The N-terminal domain of RMI1 contributes to TopoIIIα a decatenation loop in trans (marked in red, PDB ID 4CGY).

Mentions: The second key player in the dHJ dissolution reaction is TopoIIIα, which unlinks a hemicatenane intermediate during the final step of dissolution [10]. TopoIIIα belongs to the type1A class of topoisomerases, which are padlock-shaped enzymes that effect changes in DNA topology in an ATPase independent manner [31,32]. Type 1A topoisomerases are indeed markedly distinct from the ATP-dependent type-II topoisomerases and contain a 4-domain core (I-IV) that can bind, cleave and reseal single-stranded DNA substrates (Figure 1B, [33]). This process occurs through a transesterification reaction mediated by a nucleophilic tyrosine (Tyr337 in human TopoIIIα), thus creating a transient ‘DNA gate’ for nucleic-acid strand passage (between domains I and III) [34]. Type1A topoisomerases can be classified into two groups: i) relaxases (such as the E. coli TopoI), which efficiently remove negative supercoils from a covalently closed plasmid [35] and ii) decatenases (e.g. E. coli TopoIII), which can unlink catenated DNA molecules [36]. Although E. coli TopoI and TopoIII overall share the same fold, TopoIII contains small additional elements, as for example a short domain IV insertion (‘decatenation loop’), which lines the topoisomerase central cavity and is important for catenane unlinking (Figure 2A, [37,38]). Unexpectedly, TopoIIIα lacks the decatenation loop and appears structurally more similar to type1A relaxases than to decatenases [31], raising the question of how TopoIIIα-mediated hemi-catenane unlinking is achieved. Recent work indicates that RMI1 plays a key structural role in this process [31,39].


Molecular mechanism of double Holliday junction dissolution.

Swuec P, Costa A - Cell Biosci (2014)

Topoisomerase IIIα and RMI1 reconstitute a DNA decatenase. (A) Structure of the E. coli TopoI relaxase (PDB ID 1ECL) and the E. coli TopoIII decatenase (PDB ID 1D6M). TopoIII contains specific insertions lining the pore of the topoisomerase toroid which are critical for efficient decatenation. (B) Linear and three dimensional structure of RMI1 and RMI2 (PDB IDs 3NBI and 4DAY). The decatenation loop of RMI1 is highlighted in red. (C) The N-terminal domain of RMI1 contributes to TopoIIIα a decatenation loop in trans (marked in red, PDB ID 4CGY).
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4109787&req=5

Figure 2: Topoisomerase IIIα and RMI1 reconstitute a DNA decatenase. (A) Structure of the E. coli TopoI relaxase (PDB ID 1ECL) and the E. coli TopoIII decatenase (PDB ID 1D6M). TopoIII contains specific insertions lining the pore of the topoisomerase toroid which are critical for efficient decatenation. (B) Linear and three dimensional structure of RMI1 and RMI2 (PDB IDs 3NBI and 4DAY). The decatenation loop of RMI1 is highlighted in red. (C) The N-terminal domain of RMI1 contributes to TopoIIIα a decatenation loop in trans (marked in red, PDB ID 4CGY).
Mentions: The second key player in the dHJ dissolution reaction is TopoIIIα, which unlinks a hemicatenane intermediate during the final step of dissolution [10]. TopoIIIα belongs to the type1A class of topoisomerases, which are padlock-shaped enzymes that effect changes in DNA topology in an ATPase independent manner [31,32]. Type 1A topoisomerases are indeed markedly distinct from the ATP-dependent type-II topoisomerases and contain a 4-domain core (I-IV) that can bind, cleave and reseal single-stranded DNA substrates (Figure 1B, [33]). This process occurs through a transesterification reaction mediated by a nucleophilic tyrosine (Tyr337 in human TopoIIIα), thus creating a transient ‘DNA gate’ for nucleic-acid strand passage (between domains I and III) [34]. Type1A topoisomerases can be classified into two groups: i) relaxases (such as the E. coli TopoI), which efficiently remove negative supercoils from a covalently closed plasmid [35] and ii) decatenases (e.g. E. coli TopoIII), which can unlink catenated DNA molecules [36]. Although E. coli TopoI and TopoIII overall share the same fold, TopoIII contains small additional elements, as for example a short domain IV insertion (‘decatenation loop’), which lines the topoisomerase central cavity and is important for catenane unlinking (Figure 2A, [37,38]). Unexpectedly, TopoIIIα lacks the decatenation loop and appears structurally more similar to type1A relaxases than to decatenases [31], raising the question of how TopoIIIα-mediated hemi-catenane unlinking is achieved. Recent work indicates that RMI1 plays a key structural role in this process [31,39].

Bottom Line: Decatenation of double Holliday junctions, for example, is catalysed by two enzymes that work in tight coordination and belong to the same 'dissolvasome' complex.Within the dissolvasome, the RecQ-like BLM helicase provides the translocase function for Holliday junction migration, while the topoisomerase III alpha-RMI1 subcomplex works as a proficient DNA decatenase, together resulting in double-Holliday-junction unlinking.Here, we review the available architectural and biochemical knowledge on the dissolvasome machinery, with a focus on the structural interplay between its components.

View Article: PubMed Central - HTML - PubMed

Affiliation: Clare Hall laboratories, Cancer Research U.K. London Research Institute, London EN6 3LD, UK.

ABSTRACT
Processing of homologous recombination intermediates is tightly coordinated to ensure that chromosomal integrity is maintained and tumorigenesis avoided. Decatenation of double Holliday junctions, for example, is catalysed by two enzymes that work in tight coordination and belong to the same 'dissolvasome' complex. Within the dissolvasome, the RecQ-like BLM helicase provides the translocase function for Holliday junction migration, while the topoisomerase III alpha-RMI1 subcomplex works as a proficient DNA decatenase, together resulting in double-Holliday-junction unlinking. Here, we review the available architectural and biochemical knowledge on the dissolvasome machinery, with a focus on the structural interplay between its components.

No MeSH data available.


Related in: MedlinePlus