Identification of fidelity-governing factors in human recombinases DMC1 and RAD51 from cryo-EM structures
Shih-Chi Luo,
Hsin-Yi Yeh,
Wei-Hsuan Lan,
Yi-Min Wu,
Cheng-Han Yang,
Hao-Yen Chang,
Guan-Chin Su,
Chia-Yi Lee,
Wen-Jin Wu,
Hung-Wen Li,
Meng-Chiao Ho (),
Peter Chi () and
Ming-Daw Tsai ()
Additional contact information
Shih-Chi Luo: Institute of Biological Chemistry, Academia Sinica
Hsin-Yi Yeh: Institute of Biochemical Sciences, National Taiwan University
Wei-Hsuan Lan: National Taiwan University
Yi-Min Wu: Institute of Biological Chemistry, Academia Sinica
Cheng-Han Yang: Institute of Biological Chemistry, Academia Sinica
Hao-Yen Chang: Institute of Biochemical Sciences, National Taiwan University
Guan-Chin Su: Institute of Biochemical Sciences, National Taiwan University
Chia-Yi Lee: Institute of Biochemical Sciences, National Taiwan University
Wen-Jin Wu: Institute of Biological Chemistry, Academia Sinica
Hung-Wen Li: National Taiwan University
Meng-Chiao Ho: Institute of Biological Chemistry, Academia Sinica
Peter Chi: Institute of Biological Chemistry, Academia Sinica
Ming-Daw Tsai: Institute of Biological Chemistry, Academia Sinica
Nature Communications, 2021, vol. 12, issue 1, 1-10
Abstract:
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.
Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (2)
Downloads: (external link)
https://www.nature.com/articles/s41467-020-20258-1 Abstract (text/html)
Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.
Export reference: BibTeX
RIS (EndNote, ProCite, RefMan)
HTML/Text
Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20258-1
Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/
DOI: 10.1038/s41467-020-20258-1
Access Statistics for this article
Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie
More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().