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Top3-Rmi1 dissolve Rad51-mediated D loops by a topoisomerase-based mechanism.

ABSTRACT: The displacement loop (D loop) is a DNA strand invasion product formed during homologous recombination. Disruption of nascent D loops prevents recombination, and during synthesis-dependent strand annealing (SDSA), disruption of D loops extended by DNA polymerase ensures a non-crossover outcome. The proteins implicated in D loop disruption are DNA motor proteins/helicases that act by moving DNA junctions. Here we report that D loops can also be disrupted by DNA topoisomerase 3 (Top3), and this disruption depends on Top3's catalytic activity. Yeast Top3 specifically disrupts D loops mediated by yeast Rad51/Rad54; protein-free D loops or D loop mediated by bacterial RecA protein or human RAD51/RAD54 resist dissolution. Also, the human Topoisomerase IIIa-RMI1-RMI2 complex is capable of dissolving D loops. Consistent with genetic data, we suggest that the extreme growth defect and hyper-recombination phenotype of Top3-deficient yeast cells is partially a result of unprocessed D loops.

SUBMITTER: Fasching CL

PROVIDER: S-EPMC4338411 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Top3-Rmi1 dissolve Rad51-mediated D loops by a topoisomerase-based mechanism.

Fasching Clare L CL Cejka Petr P Kowalczykowski Stephen C SC Heyer Wolf-Dietrich WD

Molecular cell 20150201 4

The displacement loop (D loop) is a DNA strand invasion product formed during homologous recombination. Disruption of nascent D loops prevents recombination, and during synthesis-dependent strand annealing (SDSA), disruption of D loops extended by DNA polymerase ensures a non-crossover outcome. The proteins implicated in D loop disruption are DNA motor proteins/helicases that act by moving DNA junctions. Here we report that D loops can also be disrupted by DNA topoisomerase 3 (Top3), and this di ...[more]

PMID: 25699708

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