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

Publication ,  Journal Article
Zhu, W; Ukomadu, C; Jha, S; Senga, T; Dhar, SK; Wohlschlegel, JA; Nutt, LK; Kornbluth, S; Dutta, A
Published in: Genes & development
September 2007

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.

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Published In

Genes & development

DOI

EISSN

1549-5477

ISSN

0890-9369

Publication Date

September 2007

Volume

21

Issue

18

Start / End Page

2288 / 2299

Related Subject Headings

  • Xenopus Proteins
  • Xenopus
  • Spodoptera
  • Protein Binding
  • Models, Biological
  • Minichromosome Maintenance Proteins
  • Humans
  • HCT116 Cells
  • Developmental Biology
  • DNA-Binding Proteins
 

Citation

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Zhu, W., Ukomadu, C., Jha, S., Senga, T., Dhar, S. K., Wohlschlegel, J. A., … Dutta, A. (2007). Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication. Genes & Development, 21(18), 2288–2299. https://doi.org/10.1101/gad.1585607
Zhu, Wenge, Chinweike Ukomadu, Sudhakar Jha, Takeshi Senga, Suman K. Dhar, James A. Wohlschlegel, Leta K. Nutt, Sally Kornbluth, and Anindya Dutta. “Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication.Genes & Development 21, no. 18 (September 2007): 2288–99. https://doi.org/10.1101/gad.1585607.
Zhu W, Ukomadu C, Jha S, Senga T, Dhar SK, Wohlschlegel JA, et al. Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication. Genes & development. 2007 Sep;21(18):2288–99.
Zhu, Wenge, et al. “Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication.Genes & Development, vol. 21, no. 18, Sept. 2007, pp. 2288–99. Epmc, doi:10.1101/gad.1585607.
Zhu W, Ukomadu C, Jha S, Senga T, Dhar SK, Wohlschlegel JA, Nutt LK, Kornbluth S, Dutta A. Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication. Genes & development. 2007 Sep;21(18):2288–2299.

Published In

Genes & development

DOI

EISSN

1549-5477

ISSN

0890-9369

Publication Date

September 2007

Volume

21

Issue

18

Start / End Page

2288 / 2299

Related Subject Headings

  • Xenopus Proteins
  • Xenopus
  • Spodoptera
  • Protein Binding
  • Models, Biological
  • Minichromosome Maintenance Proteins
  • Humans
  • HCT116 Cells
  • Developmental Biology
  • DNA-Binding Proteins