A replicator-specific binding protein essential for site-specific initiation of DNA replication in mammalian cells

Mammalian chromosome replication starts from distinct sites; however, the principles governing initiation site selection are unclear because proteins essential for DNA replication do not exhibit sequence-specific DNA binding. Here we identify a replication-initiation determinant (RepID) protein that...

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Bibliographic Details
Published in:Nature communications Vol. 7; no. 1; pp. 11748 - 14
Main Authors: Zhang, Ya, Huang, Liang, Fu, Haiqing, Smith, Owen K., Lin, Chii Mei, Utani, Koichi, Rao, Mishal, Reinhold, William C., Redon, Christophe E., Ryan, Michael, Kim, RyangGuk, You, Yang, Hanna, Harlington, Boisclair, Yves, Long, Qiaoming, Aladjem, Mirit I.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 08.06.2016
Nature Publishing Group
Nature Portfolio
Subjects:
13/31
13/95
14/19
631/337/151
631/45/612/1229
Animals
Base Sequence
Binding sites
Cell cycle
Cell growth
Cell Line
Deoxyribonucleic acid
DNA
DNA Replication
DNA-Binding Proteins - metabolism
Embryo, Mammalian - cytology
Fibroblasts - metabolism
Genetic Loci
Genome
Genomes
Humanities and Social Sciences
Humans
Locus Control Region
Mammals
Mammals - metabolism
Mice
Models, Biological
multidisciplinary
Protein Binding
Proteins
Replication Origin
Science
Science (multidisciplinary)
Site selection
Yeast
United States > US
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary:Mammalian chromosome replication starts from distinct sites; however, the principles governing initiation site selection are unclear because proteins essential for DNA replication do not exhibit sequence-specific DNA binding. Here we identify a replication-initiation determinant (RepID) protein that binds a subset of replication-initiation sites. A large fraction of RepID-binding sites share a common G-rich motif and exhibit elevated replication initiation. RepID is required for initiation of DNA replication from RepID-bound replication origins, including the origin at the human beta-globin (HBB) locus. At HBB , RepID is involved in an interaction between the replication origin (Rep-P) and the locus control region. RepID-depleted murine embryonic fibroblasts exhibit abnormal replication fork progression and fewer replication-initiation events. These observations are consistent with a model, suggesting that RepID facilitates replication initiation at a distinct group of human replication origins. Origins of mammalian DNA replication are poorly characterised because they lack an Identifiable consensus sequence. Here the authors identify RepID, a protein that binds to a subset of G-rich replication origins and facilitates initiation from those origins.
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These authors contributed equally to this work
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms11748