DSSR-PyMOL cartoon-block schematics: PDB entry 8ht7

PDB-id

8ht7; DSSR-derived features in text and JSON formats

Class

DNA binding protein

Method

NMR

Summary

The n-terminal region of cdc6 specifically recognizes human DNA g-quadruplex

Reference

Geng Y, Liu C, Xu N, Shi X, Suen MC, Zhou B, Yan B, Wu C, Li H, Song Y, Chen X, Wang Z, Cai Q, Zhu G (2024): "The N-terminal region of Cdc6 specifically recognizes human DNA G-quadruplex." Int.J.Biol.Macromol., 260, 129487. doi: 10.1016/j.ijbiomac.2024.129487.

Abstract

Guanine (G)-rich nucleic acid sequences can form diverse G-quadruplex structures located in functionally significant genome regions, exerting regulatory control over essential biological processes, including DNA replication in vivo. During the initiation of DNA replication, Cdc6 is recruited by the origin recognition complex (ORC) to target specific chromosomal DNA sequences. This study reveals that human Cdc6 interacts with G-quadruplex structure through a distinct region within the N-terminal intrinsically disordered region (IDR), encompassing residues 7-20. The binding region assumes a hook-type conformation, as elucidated by the NMR solution structure in complex with htel21T₁₈. Significantly, mutagenesis and in vivo investigations confirm the highly specific nature of Cdc6's recognition of G-quadruplex. This research enhances our understanding of the fundamental mechanism governing the interaction between G-quadruplex and the N-terminal IDR region of Cdc6, shedding light on the intricate regulation of DNA replication processes.