Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication.
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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.
Cell Cycle Proteins
DNA Polymerase I
Minichromosome Maintenance Proteins
Published Version (Please cite this version)10.1101/gad.1585607
Publication InfoZhu, 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.
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Jo Rae Wright University Distinguished Professor
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
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