Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication.
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.
Type
Journal articleSubject
AnimalsCell Cycle Proteins
Cells, Cultured
Chromatin
DNA Polymerase I
DNA Replication
DNA-Binding Proteins
HCT116 Cells
Humans
Minichromosome Maintenance Proteins
Models, Biological
Protein Binding
Spodoptera
Xenopus
Xenopus Proteins
Permalink
https://hdl.handle.net/10161/8385Published Version (Please cite this version)
10.1101/gad.1585607Publication Info
Zhu, Wenge; Ukomadu, Chinweike; Jha, Sudhakar; Senga, Takeshi; Dhar, Suman K; Wohlschlegel,
James A; ... Dutta, Anindya (2007). Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA
replication. Genes Dev, 21(18). pp. 2288-2299. 10.1101/gad.1585607. Retrieved from https://hdl.handle.net/10161/8385.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
Collections
More Info
Show full item recordScholars@Duke
Sally A. Kornbluth
Jo Rae Wright University Distinguished Professor Emerita
Our lab studies the regulation of complex cellular processes, including cell cycle
progression and programmed cell death (apoptosis). These tightly orchestrated processes
are critical for appropriate cell proliferation and cell death, and when they go awry
can result in cancer and degenerative disorders. Within these larger fields, we have
focused on understanding the cellular mechanisms that prevent the onset of mitosis
prior to the completion of DNA replication, the process

Articles written by Duke faculty are made available through the campus open access policy. For more information see: Duke Open Access Policy
Rights for Collection: Scholarly Articles
Works are deposited here by their authors, and represent their research and opinions, not that of Duke University. Some materials and descriptions may include offensive content. More info
Related items
Showing items related by title, author, creator, and subject.
-
LKB1 Loss induces characteristic patterns of gene expression in human tumors associated with NRF2 activation and attenuation of PI3K-AKT.
Kaufman, Jacob M; Amann, Joseph M; Park, Kyungho; Arasada, Rajeswara Rao; Li, Haotian; Shyr, Yu; Carbone, David P (Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2014-06)Inactivation of serine/threonine kinase 11 (STK11 or LKB1) is common in lung cancer, and understanding the pathways and phenotypes altered as a consequence will aid the development of targeted therapeutic strategies. Gene ... -
Amino acid permeases require COPII components and the ER resident membrane protein Shr3p for packaging into transport vesicles in vitro.
Kuehn, MJ; Schekman, R; Ljungdahl, PO (J Cell Biol, 1996-11)In S. cerevisiae lacking SHR3, amino acid permeases specifically accumulate in membranes of the endoplasmic reticulum (ER) and fail to be transported to the plasma membrane. We examined the requirements of transport of the ... -
G protein beta gamma subunits stimulate phosphorylation of Shc adapter protein.
Touhara, K; Hawes, BE; van Biesen, T; Lefkowitz, RJ (Proc Natl Acad Sci U S A, 1995-09-26)The mechanism of mitogen-activated protein (MAP) kinase activation by pertussis toxin-sensitive Gi-coupled receptors is known to involve the beta gamma subunits of heterotrimeric G proteins (G beta gamma), p21ras activation, ...