title: Human origin recognition complex binds preferentially to G-quadruplex-preferable RNA and single-stranded DNA.
abstract: Origin recognition complex (ORC), consisting of six subunits ORC1-6, is known to bind to replication origins and function in the initiation of DNA replication in eukaryotic cells. In contrast to the fact that Saccharomyces cerevisiae ORC recognizes the replication origin in a sequence-specific manner, metazoan ORC has not exhibited strict sequence-specificity for DNA binding. Here we report that human ORC binds preferentially to G-quadruplex (G4)-preferable G-rich RNA or single-stranded DNA (ssDNA). We mapped the G-rich RNA-binding domain in the ORC1 subunit, in a region adjacent to its ATPase domain. This domain itself has an ability to preferentially recognize G4-preferable sequences of ssDNA. Furthermore, we found, by structure modeling, that the G-rich RNA-binding domain is similar to the N-terminal portion of AdoMet_MTase domain of mammalian DNA methyltransferase 1. Therefore, in contrast with the binding to double-stranded DNA, human ORC has an apparent sequence preference with respect to its RNA/ssDNA binding. Interestingly, this specificity coincides with the common signature present in most of the human replication origins. We expect that our findings provide new insights into the regulations of function and chromatin binding of metazoan ORCs.
authors.affiliation: From the Department of Chemical and Biological Sciences, Faculty of Science, Japan Women's University, Tokyo 112-8681, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Hoshina
authors.affiliation: the Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo 112-8610, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Yura
authors.affiliation: From the Department of Chemical and Biological Sciences, Faculty of Science, Japan Women's University, Tokyo 112-8681, Japan.
authors.forename: Honami
authors.initials: H
authors.lastname: Teranishi
authors.affiliation: From the Department of Chemical and Biological Sciences, Faculty of Science, Japan Women's University, Tokyo 112-8681, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Kiyasu
authors.affiliation: From the Department of Chemical and Biological Sciences, Faculty of Science, Japan Women's University, Tokyo 112-8681, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Tominaga
authors.affiliation: From the Department of Chemical and Biological Sciences, Faculty of Science, Japan Women's University, Tokyo 112-8681, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Kadoma
authors.affiliation: From the Department of Chemical and Biological Sciences, Faculty of Science, Japan Women's University, Tokyo 112-8681, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Nakatsuka
authors.affiliation: the Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan, and.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kunichika
authors.affiliation: the Division of Molecular Life Science, Graduate School of Life Science, Hokkaido University, Sapporo 001-0021, Japan.
authors.forename: Chikashi
authors.initials: C
authors.lastname: Obuse
authors.affiliation: From the Department of Chemical and Biological Sciences, Faculty of Science, Japan Women's University, Tokyo 112-8681, Japan,. Electronic address: swaga@fc.jwu.ac.jp.
authors.forename: Shou
authors.initials: S
authors.lastname: Waga
mesh_terms: D000818:Animals; D015254:DNA Modification Methylases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D009692:Nucleic Acid Heteroduplexes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051738:Origin Recognition Complex / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D014982:Xenopus laevis
chemical_list: D004277:DNA, Single-Stranded; D046912:Multiprotein Complexes; D009692:Nucleic Acid Heteroduplexes; D051738:Origin Recognition Complex; D012313:RNA; D015254:DNA Modification Methylases
keywords: DNA Methyltransferase; DNA Replication; DNA-binding Protein; G-quadruplex; ORC; Protein Structure; RNA-binding Protein; Replication Origin