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PMID:19096507

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Citation

Hartung, F, Suer, S, Knoll, A, Wurz-Wildersinn, R and Puchta, H (2008) Topoisomerase 3alpha and RMI1 suppress somatic crossovers and are essential for resolution of meiotic recombination intermediates in Arabidopsis thaliana. PLoS Genet. 4:e1000285

Abstract

Topoisomerases are enzymes with crucial functions in DNA metabolism. They are ubiquitously present in prokaryotes and eukaryotes and modify the steady-state level of DNA supercoiling. Biochemical analyses indicate that Topoisomerase 3alpha (TOP3alpha) functions together with a RecQ DNA helicase and a third partner, RMI1/BLAP75, in the resolution step of homologous recombination in a process called Holliday Junction dissolution in eukaryotes. Apart from that, little is known about the role of TOP3alpha in higher eukaryotes, as knockout mutants show early lethality or strong developmental defects. Using a hypomorphic insertion mutant of Arabidopsis thaliana (top3alpha-2), which is viable but completely sterile, we were able to define three different functions of the protein in mitosis and meiosis. The top3alpha-2 line exhibits fragmented chromosomes during mitosis and sensitivity to camptothecin, suggesting an important role in chromosome segregation partly overlapping with that of type IB topoisomerases. Furthermore, AtTOP3alpha, together with AtRECQ4A and AtRMI1, is involved in the suppression of crossover recombination in somatic cells as well as DNA repair in both mammals and A. thaliana. Surprisingly, AtTOP3alpha is also essential for meiosis. The phenotype of chromosome fragmentation, bridges, and telophase I arrest can be suppressed by AtSPO11 and AtRAD51 mutations, indicating that the protein is required for the resolution of recombination intermediates. As Atrmi1 mutants have a similar meiotic phenotype to Attop3alpha mutants, both proteins seem to be involved in a mechanism safeguarding the entangling of homologous chromosomes during meiosis. The requirement of AtTOP3alpha and AtRMI1 in a late step of meiotic recombination strongly hints at the possibility that the dissolution of double Holliday Junctions via a hemicatenane intermediate is indeed an indispensable step of meiotic recombination.

Links

PubMed PMC2588661 Online version:10.1371/journal.pgen.1000285

Keywords

Arabidopsis/cytology; Arabidopsis/genetics; Arabidopsis/metabolism; Arabidopsis Proteins/genetics; Arabidopsis Proteins/metabolism; Carrier Proteins/genetics; Carrier Proteins/metabolism; Crossing Over, Genetic; DNA Topoisomerases, Type I/genetics; DNA Topoisomerases, Type I/metabolism; Meiosis; Molecular Sequence Data; Mutagenesis, Insertional; Phenotype; Recombination, Genetic

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

ARATH:B3H7H7

acts_upstream_of_or_within

GO:0051321: meiotic cell cycle

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

ARATH:RMI1

involved_in

GO:0000712: resolution of meiotic recombination intermediates

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

ARATH:TOP3A

acts_upstream_of_or_within

GO:0000712: resolution of meiotic recombination intermediates

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

ARATH:TOP3A

acts_upstream_of_or_within

GO:0000278: mitotic cell cycle

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

ARATH:TOP3A

acts_upstream_of_or_within

GO:0007059: chromosome segregation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

ARATH:TOP3A

acts_upstream_of_or_within

GO:0006281: DNA repair

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

ARATH:TOP3A

acts_upstream_of_or_within

GO:0051321: meiotic cell cycle

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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