7C98

Human DMC1 post-synaptic complexes

Summary for 7C98

• Entry DOI: 10.2210/pdb7c98/pdb
• EMDB information: 30308
• Descriptor: Meiotic recombination protein DMC1/LIM15 homolog, DNA (5'-D(P*TP*TP*TP*TP*TP*TP*TP*TP*T)-3'), DNA (5'-D(P*AP*AP*AP*AP*AP*AP*AP*AP*A)-3'), ... (5 entities in total)
• Functional Keywords: meiotic homologous recombination, dna repair, atpase, recombination, recombination-dna complex, recombination/dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 120298.60

Authors

Luo, S.C.,Yeh, H.Y.,Chi, P.,Ho, M.C.,Tsai, M.D. (deposition date: 2020-06-05, release date: 2020-11-18, Last modification date: 2024-03-27)

Primary citation

Luo, S.C.,Yeh, H.Y.,Lan, W.H.,Wu, Y.M.,Yang, C.H.,Chang, H.Y.,Su, G.C.,Lee, C.Y.,Wu, W.J.,Li, H.W.,Ho, M.C.,Chi, P.,Tsai, M.D.
Identification of fidelity-governing factors in human recombinases DMC1 and RAD51 from cryo-EM structures.
Nat Commun, 12:115-115, 2021

PubMed Abstract: 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.

PubMed: 33446654
DOI: 10.1038/s41467-020-20258-1

Experimental method

ELECTRON MICROSCOPY (3.47 Å)