Investigation of the Interaction of Human Origin Recognition Complex Subunit 1 with G-Quadruplex DNAs of Human c-myc Promoter and Telomere Regions

International Journal of Molecular Sciences

卷:22

Shou Waga¹  Haruka Horinouchi¹  Shoko Hoshina¹  Afaf Eladl²  Keiko Kondo²  Takashi Nagata²  Masato Katahira²  Yudai Yamaoki² 

[1] Department of Chemical and Biological Sciences, Japan Women’s University, Tokyo 112-8681, Japan;

[2] Institute of Advanced Energy, Kyoto University, Kyoto 611-0011, Japan;

关键词: origin recognition complex;    G-quadruplex;    DNA replication;    replication origin;    NMR;    structure;   

DOI  :  10.3390/ijms22073481

来源: DOAJ

【 摘 要 】

Origin recognition complex (ORC) binds to replication origins in eukaryotic DNAs and plays an important role in replication. Although yeast ORC is known to sequence-specifically bind to a replication origin, how human ORC recognizes a replication origin remains unknown. Previous genome-wide studies revealed that guanine (G)-rich sequences, potentially forming G-quadruplex (G4) structures, are present in most replication origins in human cells. We previously suggested that the region comprising residues 413–511 of human ORC subunit 1, hORC1^413–511, binds preferentially to G-rich DNAs, which form a G4 structure in the absence of hORC1^413–511. Here, we investigated the interaction of hORC1^413-511 with various G-rich DNAs derived from human c-myc promoter and telomere regions. Fluorescence anisotropy revealed that hORC1^413–511 binds preferentially to DNAs that have G4 structures over ones having double-stranded structures. Importantly, circular dichroism (CD) and nuclear magnetic resonance (NMR) showed that those G-rich DNAs retain the G4 structures even after binding with hORC1^413–511. NMR chemical shift perturbation analyses revealed that the external G-tetrad planes of the G4 structures are the primary binding sites for hORC1^413–511. The present study suggests that human ORC1 may recognize replication origins through the G4 structure.

【 授权许可】

Unknown