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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 595-606 |
| Number of pages | 12 |
| Journal | Molecular Cell |
| Volume | 57 |
| Issue number | 4 |
| DOIs | |
| State | Published - Feb 19 2015 |
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ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
Cite this
Top3-Rmi1 dissolve Rad51-mediated D loops by a topoisomerase-based mechanism. / Fasching, Clare L.; Cejka, Petr; Kowalczykowski, Stephen C.; Heyer, Wolf Dietrich.
In: Molecular Cell, Vol. 57, No. 4, 19.02.2015, p. 595-606.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Top3-Rmi1 dissolve Rad51-mediated D loops by a topoisomerase-based mechanism
AU - Fasching, Clare L.
AU - Cejka, Petr
AU - Kowalczykowski, Stephen C.
AU - Heyer, Wolf Dietrich
PY - 2015/2/19
Y1 - 2015/2/19
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84923838375&partnerID=8YFLogxK
U2 - 10.1016/j.molcel.2015.01.022
DO - 10.1016/j.molcel.2015.01.022
M3 - Article
C2 - 25699708
AN - SCOPUS:84923838375
VL - 57
SP - 595
EP - 606
JO - Molecular Cell
JF - Molecular Cell
SN - 1097-2765
IS - 4
ER -