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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| Vydáno v: | Nature communications Ročník 7; číslo 1; s. 11748 - 14 |
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| Hlavní autoři: | , , , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
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London
Nature Publishing Group UK
08.06.2016
Nature Publishing Group Nature Portfolio |
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| ISSN: | 2041-1723, 2041-1723 |
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| Abstract | 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. |
|---|---|
| AbstractList | 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. 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.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. 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. 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. 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. 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. |
| ArticleNumber | 11748 |
| Author | Ryan, Michael Huang, Liang Hanna, Harlington Boisclair, Yves Kim, RyangGuk Rao, Mishal Reinhold, William C. Zhang, Ya Lin, Chii Mei Smith, Owen K. Redon, Christophe E. Fu, Haiqing Utani, Koichi Long, Qiaoming You, Yang Aladjem, Mirit I. |
| Author_xml | – sequence: 1 givenname: Ya surname: Zhang fullname: Zhang, Ya organization: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health – sequence: 2 givenname: Liang orcidid: 0000-0003-1663-7025 surname: Huang fullname: Huang, Liang organization: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health – sequence: 3 givenname: Haiqing surname: Fu fullname: Fu, Haiqing organization: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health – sequence: 4 givenname: Owen K. surname: Smith fullname: Smith, Owen K. organization: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health – sequence: 5 givenname: Chii Mei surname: Lin fullname: Lin, Chii Mei organization: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health – sequence: 6 givenname: Koichi surname: Utani fullname: Utani, Koichi organization: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health – sequence: 7 givenname: Mishal surname: Rao fullname: Rao, Mishal organization: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health – sequence: 8 givenname: William C. surname: Reinhold fullname: Reinhold, William C. organization: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health – sequence: 9 givenname: Christophe E. surname: Redon fullname: Redon, Christophe E. organization: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health – sequence: 10 givenname: Michael surname: Ryan fullname: Ryan, Michael organization: In Silico Solutions – sequence: 11 givenname: RyangGuk surname: Kim fullname: Kim, RyangGuk organization: In Silico Solutions – sequence: 12 givenname: Yang surname: You fullname: You, Yang organization: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health – sequence: 13 givenname: Harlington surname: Hanna fullname: Hanna, Harlington organization: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health – sequence: 14 givenname: Yves surname: Boisclair fullname: Boisclair, Yves organization: Department of Animal Science, Cornell University – sequence: 15 givenname: Qiaoming surname: Long fullname: Long, Qiaoming organization: Department of Animal Science, Cornell University – sequence: 16 givenname: Mirit I. surname: Aladjem fullname: Aladjem, Mirit I. email: aladjemm@mail.nih.gov organization: Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/27272143$$D View this record in MEDLINE/PubMed |
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| Snippet | Mammalian chromosome replication starts from distinct sites; however, the principles governing initiation site selection are unclear because proteins essential... Origins of mammalian DNA replication are poorly characterised because they lack an Identifiable consensus sequence. Here the authors identify RepID, a protein... |
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| SubjectTerms | 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 |
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| Title | A replicator-specific binding protein essential for site-specific initiation of DNA replication in mammalian cells |
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