Esc4p, a new target of Mec1p (ATR), promotes resumption of DNA synthesis after DNA damage

    Research output: Contribution to journalArticle

    75 Citations (Scopus)

    Abstract

    The DNA damage-responsive protein kinases ATM and ATR phosphorylate SQ/TQ motifs that lie in clusters in most of their in vivo targets. Budding yeast Esc4p contains a cluster of SQ/TQ motifs, suggesting that it might be a target of Mec1p/Tel1p (yeast ATR/ATM). Here it is reported that Esc4p is phosphorylated by Mec1p in response to DNA damage during DNA replication and that cells lacking Esc4p are hypersensitive to DNA damage specifically during S phase. Esc4p is not required for the intra-S-phase checkpoint but is essential for resumption of chromosome replication after DNA damage, and its role in promoting restart appears to be distinct from that of Rad53p. Mutation of Esc4p SQ/TQ motifs phosphorylated by Mec1p or mutation of the BRCT domains of Esc4p also renders cells unable to restart DNA replication after DNA damage and causes hypersensitivity to genotoxins. These results identify Esc4p as an important new S-phase-specific target of Mec1p.
    Original languageEnglish
    Pages (from-to)1188-1197
    Number of pages10
    JournalThe EMBO Journal
    Volume23
    Issue number5
    DOIs
    Publication statusPublished - 2004

    Fingerprint

    DNA Damage
    S Phase Cell Cycle Checkpoints
    DNA
    DNA Replication
    S Phase
    Automatic teller machines
    Yeast
    Mutation
    Saccharomycetales
    Mutagens
    Protein Kinases
    Hypersensitivity
    Chromosomes
    Yeasts

    Keywords

    • ATR
    • DNA damage
    • Esc4p
    • Mec1p

    Cite this

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    title = "Esc4p, a new target of Mec1p (ATR), promotes resumption of DNA synthesis after DNA damage",
    abstract = "The DNA damage-responsive protein kinases ATM and ATR phosphorylate SQ/TQ motifs that lie in clusters in most of their in vivo targets. Budding yeast Esc4p contains a cluster of SQ/TQ motifs, suggesting that it might be a target of Mec1p/Tel1p (yeast ATR/ATM). Here it is reported that Esc4p is phosphorylated by Mec1p in response to DNA damage during DNA replication and that cells lacking Esc4p are hypersensitive to DNA damage specifically during S phase. Esc4p is not required for the intra-S-phase checkpoint but is essential for resumption of chromosome replication after DNA damage, and its role in promoting restart appears to be distinct from that of Rad53p. Mutation of Esc4p SQ/TQ motifs phosphorylated by Mec1p or mutation of the BRCT domains of Esc4p also renders cells unable to restart DNA replication after DNA damage and causes hypersensitivity to genotoxins. These results identify Esc4p as an important new S-phase-specific target of Mec1p.",
    keywords = "ATR, DNA damage, Esc4p, Mec1p",
    author = "John Rouse",
    note = "dc.publisher: Nature Publishing Group",
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    language = "English",
    volume = "23",
    pages = "1188--1197",
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    Esc4p, a new target of Mec1p (ATR), promotes resumption of DNA synthesis after DNA damage. / Rouse, John.

    In: The EMBO Journal, Vol. 23, No. 5, 2004, p. 1188-1197.

    Research output: Contribution to journalArticle

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    AU - Rouse, John

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    N2 - The DNA damage-responsive protein kinases ATM and ATR phosphorylate SQ/TQ motifs that lie in clusters in most of their in vivo targets. Budding yeast Esc4p contains a cluster of SQ/TQ motifs, suggesting that it might be a target of Mec1p/Tel1p (yeast ATR/ATM). Here it is reported that Esc4p is phosphorylated by Mec1p in response to DNA damage during DNA replication and that cells lacking Esc4p are hypersensitive to DNA damage specifically during S phase. Esc4p is not required for the intra-S-phase checkpoint but is essential for resumption of chromosome replication after DNA damage, and its role in promoting restart appears to be distinct from that of Rad53p. Mutation of Esc4p SQ/TQ motifs phosphorylated by Mec1p or mutation of the BRCT domains of Esc4p also renders cells unable to restart DNA replication after DNA damage and causes hypersensitivity to genotoxins. These results identify Esc4p as an important new S-phase-specific target of Mec1p.

    AB - The DNA damage-responsive protein kinases ATM and ATR phosphorylate SQ/TQ motifs that lie in clusters in most of their in vivo targets. Budding yeast Esc4p contains a cluster of SQ/TQ motifs, suggesting that it might be a target of Mec1p/Tel1p (yeast ATR/ATM). Here it is reported that Esc4p is phosphorylated by Mec1p in response to DNA damage during DNA replication and that cells lacking Esc4p are hypersensitive to DNA damage specifically during S phase. Esc4p is not required for the intra-S-phase checkpoint but is essential for resumption of chromosome replication after DNA damage, and its role in promoting restart appears to be distinct from that of Rad53p. Mutation of Esc4p SQ/TQ motifs phosphorylated by Mec1p or mutation of the BRCT domains of Esc4p also renders cells unable to restart DNA replication after DNA damage and causes hypersensitivity to genotoxins. These results identify Esc4p as an important new S-phase-specific target of Mec1p.

    KW - ATR

    KW - DNA damage

    KW - Esc4p

    KW - Mec1p

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