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PDBsum entry 7c9c
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Recombination/DNA
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PDB id
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7c9c
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References listed in PDB file
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Key reference
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Title
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Identification of fidelity-Governing factors in human recombinases dmc1 and rad51 from cryo-Em structures.
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Authors
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S.C.Luo,
H.Y.Yeh,
W.H.Lan,
Y.M.Wu,
C.H.Yang,
H.Y.Chang,
G.C.Su,
C.Y.Lee,
W.J.Wu,
H.W.Li,
M.C.Ho,
P.Chi,
M.D.Tsai.
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Ref.
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Nat Commun, 2021,
12,
115.
[DOI no: ]
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PubMed id
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Abstract
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Both high-fidelity and mismatch-tolerant recombination, catalyzed by RAD51 and
DMC1 recombinases, respectively, are indispensable for genomic integrity. Here,
we use cryo-EM, MD simulation and functional analysis to elucidate the
structural basis for the mismatch tolerance of DMC1. Structural analysis of DMC1
presynaptic and postsynaptic complexes suggested that the lineage-specific Loop
1 Gln244 (Met243 in RAD51) may help stabilize DNA backbone, whereas Loop 2
Pro274 and Gly275 (Val273/Asp274 in RAD51) may provide an open "triplet
gate" for mismatch tolerance. In support, DMC1-Q244M displayed marked
increase in DNA dynamics, leading to unobservable DNA map. MD simulation showed
highly dispersive mismatched DNA ensemble in RAD51 but well-converged DNA in
DMC1 and RAD51-V273P/D274G. Replacing Loop 1 or Loop 2 residues in DMC1 with
RAD51 counterparts enhanced DMC1 fidelity, while reciprocal mutations in RAD51
attenuated its fidelity. Our results show that three Loop 1/Loop 2 residues
jointly enact contrasting fidelities of DNA recombinases.
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