The Rad51 paralog complex Rad55-Rad57 acts as a molecular chaperone during homologous recombination
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
The Rad51 paralog complex Rad55-Rad57 acts as a molecular chaperone during homologous recombination. / Roy, Upasana; Kwon, Youngho; Marie, Lea; Symington, Lorraine; Sung, Patrick; Lisby, Michael; Greene, Eric C.
In: Molecular Cell, Vol. 81, No. 5, 2021, p. 1043-1057.e8.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - The Rad51 paralog complex Rad55-Rad57 acts as a molecular chaperone during homologous recombination
AU - Roy, Upasana
AU - Kwon, Youngho
AU - Marie, Lea
AU - Symington, Lorraine
AU - Sung, Patrick
AU - Lisby, Michael
AU - Greene, Eric C.
PY - 2021
Y1 - 2021
N2 - Homologous recombination (HR) is essential for maintenance of genome integrity. Rad51 paralogs fulfill a conserved but undefined role in HR, and their mutations are associated with increased cancer risk in humans. Here, we use single-molecule imaging to reveal that the Saccharomyces cerevisiae Rad51 paralog complex Rad55-Rad57 promotes assembly of Rad51 recombinase filament through transient interactions, providing evidence that it acts like a classical molecular chaperone. Srs2 is an ATP-dependent anti-recombinase that downregulates HR by actively dismantling Rad51 filaments. Contrary to the current model, we find that Rad55-Rad57 does not physically block the movement of Srs2. Instead, Rad55-Rad57 promotes rapid re-assembly of Rad51 filaments after their disruption by Srs2. Our findings support a model in which Rad51 is in flux between free and single-stranded DNA (ssDNA)-bound states, the rate of which is controlled dynamically though the opposing actions of Rad55-Rad57 and Srs2. Roy et al. present a single-molecule analysis of the Rad51 paralog complex Rad55-Rad57. They show that Rad55-Rad57 binds transiently to Rad51-ssDNA to promote Rad51 filament assembly but then dissociates quickly as the filaments mature. They further demonstrate that Rad55-Rad57 does not block the translocase Srs2.
AB - Homologous recombination (HR) is essential for maintenance of genome integrity. Rad51 paralogs fulfill a conserved but undefined role in HR, and their mutations are associated with increased cancer risk in humans. Here, we use single-molecule imaging to reveal that the Saccharomyces cerevisiae Rad51 paralog complex Rad55-Rad57 promotes assembly of Rad51 recombinase filament through transient interactions, providing evidence that it acts like a classical molecular chaperone. Srs2 is an ATP-dependent anti-recombinase that downregulates HR by actively dismantling Rad51 filaments. Contrary to the current model, we find that Rad55-Rad57 does not physically block the movement of Srs2. Instead, Rad55-Rad57 promotes rapid re-assembly of Rad51 filaments after their disruption by Srs2. Our findings support a model in which Rad51 is in flux between free and single-stranded DNA (ssDNA)-bound states, the rate of which is controlled dynamically though the opposing actions of Rad55-Rad57 and Srs2. Roy et al. present a single-molecule analysis of the Rad51 paralog complex Rad55-Rad57. They show that Rad55-Rad57 binds transiently to Rad51-ssDNA to promote Rad51 filament assembly but then dissociates quickly as the filaments mature. They further demonstrate that Rad55-Rad57 does not block the translocase Srs2.
KW - DNA curtains
KW - DNA repair
KW - homologous recombination
KW - Rad51
KW - Rad51 paralogs
KW - Rad55-Rad57
KW - single-molecule
KW - Srs2
U2 - 10.1016/j.molcel.2020.12.019
DO - 10.1016/j.molcel.2020.12.019
M3 - Journal article
C2 - 33421364
AN - SCOPUS:85099707790
VL - 81
SP - 1043-1057.e8
JO - Molecular Cell
JF - Molecular Cell
SN - 1097-2765
IS - 5
ER -
ID: 256068752