We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Human cytomegalovirus prevents replication licensing by inhibiting MCM loading onto chromatin.
- Authors
Wiebusch, Lüder; Uecker, Ralf; Hagemeier, Christian
- Abstract
To allow DNA replication only once per cell cycle, origins of replication are reactivated ('licensed') during each G1 phase. Licensing is facilitated by assembly of the pre-replicative complex (pre-RC) at origins that concludes with loading the mini-chromosome maintenance (MCM) complex onto chromatin. Here we show that a virus exploits pre-RC assembly to selectively inhibit cellular DNA replication. Infection of quiescent primary fibroblasts with human cytomegalovirus (HCMV) induces all pre-RC factors. Although this is sufficient to assemble the MCM-loading factors onto chromatin, as it is in serum-stimulated cells, the virus inhibits loading of the MCM complex itself, thereby prematurely abrogating replication licensing. This provides a new level of control in pre-RC assembly and a mechanistic rationale for the unusual HCMV-induced G1 arrest that occurs despite the activation of the cyclin E-dependent transcription programme. Thus, this particularly large virus might thereby secure the supply with essential replication factors but omit competitive cellular DNA replication.
- Publication
EMBO reports, 2003, Vol 4, Issue 1, p42
- ISSN
1469-221X
- Publication type
Journal Article
- DOI
10.1038/sj.embor.embor707