7CGY

Human DMC1 Q244M mutant of the post-synaptic complexes

Summary for 7CGY

• Entry DOI: 10.2210/pdb7cgy/pdb
• EMDB information: 30366
• Descriptor: Meiotic recombination protein DMC1/LIM15 homolog, CALCIUM ION, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER (3 entities in total)
• Functional Keywords: meiotic homologous recombination, dna repair, atpase, recombination
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 3
• Total formula weight: 114841.12

Authors

Chi, H.Y.,Ho, M.C.,Tsai, M.D.,Luo, S.C.,Yeh, H.Y. (deposition date: 2020-07-03, 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 (3.2 Å)