Structural Basis of Sequence-specific Holliday Junction Cleavage by MOC1

Overview

Journal Nat Chem Biol

Specialties Biochemistry
Biology
Chemistry

Date 2019 Oct 16

PMID 31611704

Citations 12

Authors

Huajian Lin

Danping Zhang

Ke Zuo

Cai Yuan

Jinyu Li

Mingdong Huang

Zhonghui Lin

Affiliations

Soon will be listed here.

Abstract

The Holliday junction (HJ) is a key intermediate during homologous recombination and DNA double-strand break repair. Timely HJ resolution by resolvases is critical for maintaining genome stability. The mechanisms underlying sequence-specific substrate recognition and cleavage by resolvases remain elusive. The monokaryotic chloroplast 1 protein (MOC1) specifically cleaves four-way DNA junctions in a sequence-specific manner. Here, we report the crystal structures of MOC1 from Zea mays, alone or bound to HJ DNA. MOC1 uses a unique β-hairpin to embrace the DNA junction. A base-recognition motif specifically interacts with the junction center, inducing base flipping and pseudobase-pair formation at the strand-exchanging points. Structures of MOC1 bound to HJ and different metal ions support a two-metal ion catalysis mechanism. Further molecular dynamics simulations and biochemical analyses reveal a communication between specific substrate recognition and metal ion-dependent catalysis. Our study thus provides a mechanism for how a resolvase turns substrate specificity into catalytic efficiency.

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