PDBsum entry 7c9c

Recombination/DNA

PDB id: 7c9c

Contents

Protein chains

308 a.a.

DNA/RNA

Ligands

ANP ×3

Metals

_CA ×3

PDB id:

7c9c

Name:

Recombination/DNA

Title:

Human dmc1 pre-synaptic complexes

Structure:

DNA (5'-d(p Tp Tp Tp Tp Tp Tp Tp Tp T)-3'). Chain: d. Engineered: yes. Meiotic recombination protein dmc1/lim15 homolog. Chain: a, b, c. Engineered: yes

Source:

Synthetic: yes. Synthetic construct. Organism_taxid: 32630. Homo sapiens. Human. Organism_taxid: 9606. Gene: dmc1, dmc1h, lim15. Expressed in: escherichia coli. Expression_system_taxid: 562.

Authors:

S.C.Luo,H.Y.Yeh,P.Chi,M.C.Ho,M.D.Tsai

Key ref:

S.C.Luo et al. (2021). Identification of fidelity-governing factors in human recombinases DMC1 and RAD51 from cryo-EM structures. Nat Commun, 12, 115. PubMed id: 33446654 DOI: 10.1038/s41467-020-20258-1

Date:

05-Jun-20 Release date: 25-Nov-20

Protein chains

Q14565  (DMC1_HUMAN) -  Meiotic recombination protein DMC1/LIM15 homolog from Homo sapiens

Seq: 340 a.a.

Struc: 308 a.a.

DNA/RNA chain

T-T-T-T-T-T-T-T-T 9 bases

DOI no: 10.1038/s41467-020-20258-1

Nat Commun 12:115 (2021)

PubMed id: 33446654

Identification of fidelity-governing factors in human recombinases DMC1 and RAD51 from cryo-EM structures.

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.

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.