Deregulated replication licensing causes DNA fragmentation consistent with head-to-tail fork collision

Iain F. Davidson, Anatoliy Li, J. Julian Blow

    Research output: Contribution to journalArticle

    98 Citations (Scopus)

    Abstract

    Correct regulation of the replication licensing system ensures that no DNA is rereplicated in a single cell cycle. When the licensing protein Cdt1 is overexpressed in G2 phase of the cell cycle, replication origins are relicensed and the DNA is rereplicated. At the same time, checkpoint pathways are activated that block further cell cycle progression. We have studied the consequence of deregulating the licensing system by adding recombinant Cdt1 to Xenopus egg extracts. We show that Cdt1 induces checkpoint activation and the appearance of small fragments of double-stranded DNA. DNA fragmentation and strong checkpoint activation are dependent on uncontrolled rereplication and do not occur after a single coordinated round of rereplication. The DNA fragments are composed exclusively of rereplicated DNA. The unusual characteristics of these fragments suggest that they result from head-to-tail collision (rear ending) of replication forks chasing one another along the same DNA template.
    Original languageEnglish
    Pages (from-to)433-443
    Number of pages11
    JournalMolecular Cell
    Volume24
    Issue number3
    DOIs
    Publication statusPublished - Nov 2006

    Keywords

    • DNA
    • DNA fragmentation
    • DNA replication genetics
    • Xenopus metabolism

    Fingerprint Dive into the research topics of 'Deregulated replication licensing causes DNA fragmentation consistent with head-to-tail fork collision'. Together they form a unique fingerprint.

  • Cite this