Functional Cooperation Between FACT and MCM Helicase Facilitates Initiation of Chromatin DNA Replication

EMBO J. 2006 Sep 6;25(17):3975-85. doi: 10.1038/sj.emboj.7601271. Epub 2006 Aug 10.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatin / genetics*
  • DNA Helicases / metabolism*
  • DNA Replication / physiology*
  • DNA-Binding Proteins / metabolism*
  • Enzyme Activation
  • HeLa Cells
  • High Mobility Group Proteins / metabolism*
  • Humans
  • Nucleosomes / metabolism
  • Protein Binding
  • Recombinant Proteins / metabolism
  • Replication Origin
  • S Phase / physiology
  • Transcriptional Elongation Factors / metabolism*

Substances

  • Chromatin
  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • Nucleosomes
  • Recombinant Proteins
  • SSRP1 protein, human
  • Transcriptional Elongation Factors
  • DNA Helicases