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  • The EMBO Journal (2006) 25, 3975 - 3985
  • doi:10.1038/sj.emboj.7601271

Published online: 10 August 2006

Functional cooperation between FACT and MCM helicase facilitates initiation of chromatin DNA replication

Bertrand Chin-Ming Tan1, Cheng-Ting Chien2, Susumu Hirose3 and Sheng-Chung Lee1,4

  1. Institute of Molecular Medicine, National Taiwan University, Taipei, Taiwan
  2. Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan
  3. Department of Developmental Genetics, National Institute of Genetics, Mishima, Shizuokaken, Japan
  4. Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan

Correspondence to:

Sheng-Chung Lee, Institute of Molecular Medicine, National Taiwan University, 7 Chung Shan South Road, Taipei, Taiwan. Tel.: +886 2 2356 2982; Fax: +886 2 2395 7801; E-mail: slee@ntu.edu.tw

Received 1 March 2006; Accepted 18 July 2006

Chromatin is suppressive in nature to cellular enzymes that metabolize DNA, mainly due to the inherent inaccessibility of the DNA template. Despite extensive understanding of the involvement of chromatin-modifying factors in transcription, roles of related activities in DNA replication remain largely elusive. Here, we show that the heterodimeric transcriptional elongation factor FACT (facilitates chromatin transcription) is functionally linked to DNA synthesis. Its involvement in DNA replication is partly mediated by the stable association with the replicative helicase complex, MCM, and further by the coexistence with MCM on replication origin. Furthermore, relying on its nucleosome-reorganizing activity, FACT can facilitate chromatin unwinding by the MCM complex, which is otherwise inert on the nucleosomal template. As a consequence, the physical and functional interaction between FACT and MCM is an important determinant in the proper initiation of DNA replication and S phase in vivo. Together, our findings identify FACT as an integral and conserved component of the endogenous replication machinery, and support a model in which the concerted action of helicase and chromatin-modifying activities promotes chromosome replication.

  • Keywords:

    • chromatin,
    • DNA replication,
    • FACT,
    • MCM helicase,
    • S phase