Mrc1 and Tof1 promote replication fork progression and recovery independently of Rad53

Helene Tourriere, Gwennaëlle Versini, Violeta Cordón-Preciado, Constance Alabert, Philippe Pasero (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    221 Citations (Scopus)

    Abstract

    The yeast checkpoint factors Mrc1p and Tof1p travel with the replication fork and mediate the activation of the Rad53p kinase in response to a replication stress. We show here that both proteins are required for normal fork progression but play different roles at stalled forks. Tof1p is critical for the activity of the rDNA replication fork barrier (RFB) but plays a minor role in the replication checkpoint. In contrast, Mrc1p is not necessary for RFB activity but is essential to mediate the replication stress response. Interestingly, stalled forks did not collapse in mrc1Δ cells exposed to hydroxyurea (HU) as they do in rad53 mutants. However, forks failed to restart when mrc1Δ cells were released from the block. The critical role of Mrc1p in HU is therefore to promote fork recovery in a Rad53p-independent manner, presumably through the formation of a stable fork-pausing complex.
    Original languageEnglish
    Pages (from-to)699-706
    Number of pages8
    JournalMolecular Cell
    Volume19
    Issue number5
    DOIs
    Publication statusPublished - 2 Sept 2005

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