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Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication.

dc.contributor.author Dhar, Suman K
dc.contributor.author Dutta, A
dc.contributor.author Jha, S
dc.contributor.author Kornbluth, S
dc.contributor.author Nutt, LK
dc.contributor.author Senga, T
dc.contributor.author Ukomadu, C
dc.contributor.author Wohlschlegel, JA
dc.contributor.author Zhu, Wenge
dc.coverage.spatial United States
dc.date.accessioned 2014-03-06T16:57:29Z
dc.date.issued 2007-09-15
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/17761813
dc.identifier gad.1585607
dc.identifier.issn 0890-9369
dc.identifier.uri https://hdl.handle.net/10161/8385
dc.description.abstract The MCM2-7 helicase complex is loaded on DNA replication origins during the G1 phase of the cell cycle to license the origins for replication in S phase. How the initiator primase-polymerase complex, DNA polymerase alpha (pol alpha), is brought to the origins is still unclear. We show that And-1/Ctf4 (Chromosome transmission fidelity 4) interacts with Mcm10, which associates with MCM2-7, and with the p180 subunit of DNA pol alpha. And-1 is essential for DNA synthesis and the stability of p180 in mammalian cells. In Xenopus egg extracts And-1 is loaded on the chromatin after Mcm10, concurrently with DNA pol alpha, and is required for efficient DNA synthesis. Mcm10 is required for chromatin loading of And-1 and an antibody that disrupts the Mcm10-And-1 interaction interferes with the loading of And-1 and of pol alpha, inhibiting DNA synthesis. And-1/Ctf4 is therefore a new replication initiation factor that brings together the MCM2-7 helicase and the DNA pol alpha-primase complex, analogous to the linker between helicase and primase or helicase and polymerase that is seen in the bacterial replication machinery. The discovery also adds to the connection between replication initiation and sister chromatid cohesion.
dc.language eng
dc.relation.ispartof Genes Dev
dc.relation.isversionof 10.1101/gad.1585607
dc.subject Animals
dc.subject Cell Cycle Proteins
dc.subject Cells, Cultured
dc.subject Chromatin
dc.subject DNA Polymerase I
dc.subject DNA Replication
dc.subject DNA-Binding Proteins
dc.subject HCT116 Cells
dc.subject Humans
dc.subject Minichromosome Maintenance Proteins
dc.subject Models, Biological
dc.subject Protein Binding
dc.subject Spodoptera
dc.subject Xenopus
dc.subject Xenopus Proteins
dc.title Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication.
dc.type Journal article
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/17761813
pubs.begin-page 2288
pubs.end-page 2299
pubs.issue 18
pubs.organisational-group Basic Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Pharmacology & Cancer Biology
pubs.organisational-group School of Medicine
pubs.publication-status Published
pubs.volume 21


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