How dormant origins promote complete genome replication

J. Julian Blow, Xin Quan Ge, Dean A. Jackson

    Research output: Contribution to journalReview article

    126 Citations (Scopus)

    Abstract

    Many replication origins that are licensed by loading MCM2-7 complexes in G1 are not normally used. Activation of these dormant origins during S phase provides a first line of defence for the genome if replication is inhibited. When replication forks fail, dormant origins are activated within regions of the genome currently engaged in replication. At the same time, DNA damage-response kinases activated by the stalled forks preferentially suppress the assembly of new replication factories, thereby ensuring that chromosomal regions experiencing replicative stress complete synthesis before new regions of the genome are replicated. Mice expressing reduced levels of MCM2-7 have fewer dormant origins, are cancer-prone and are genetically unstable, demonstrating the importance of dormant origins for preserving genome integrity. We review the function of dormant origins, the molecular mechanism of their regulation and their physiological implications.

    Original languageEnglish
    Pages (from-to)405-414
    Number of pages10
    JournalTrends in Biochemical Sciences
    Volume36
    Issue number8
    DOIs
    Publication statusPublished - Aug 2011

    Keywords

    • EUKARYOTIC DNA-REPLICATION
    • XENOPUS EGG EXTRACTS
    • HUMAN-CELLS
    • S-PHASE
    • MCM PROTEINS
    • CHECKPOINT RESPONSES
    • FACTORY ACTIVATION
    • ULTRAVIOLET-LIGHT
    • TUMOR SUPPRESSION
    • LICENSING SYSTEM

    Cite this

    Blow, J. Julian ; Ge, Xin Quan ; Jackson, Dean A. / How dormant origins promote complete genome replication. In: Trends in Biochemical Sciences. 2011 ; Vol. 36, No. 8. pp. 405-414.
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    How dormant origins promote complete genome replication. / Blow, J. Julian; Ge, Xin Quan; Jackson, Dean A.

    In: Trends in Biochemical Sciences, Vol. 36, No. 8, 08.2011, p. 405-414.

    Research output: Contribution to journalReview article

    TY - JOUR

    T1 - How dormant origins promote complete genome replication

    AU - Blow, J. Julian

    AU - Ge, Xin Quan

    AU - Jackson, Dean A.

    PY - 2011/8

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    N2 - Many replication origins that are licensed by loading MCM2-7 complexes in G1 are not normally used. Activation of these dormant origins during S phase provides a first line of defence for the genome if replication is inhibited. When replication forks fail, dormant origins are activated within regions of the genome currently engaged in replication. At the same time, DNA damage-response kinases activated by the stalled forks preferentially suppress the assembly of new replication factories, thereby ensuring that chromosomal regions experiencing replicative stress complete synthesis before new regions of the genome are replicated. Mice expressing reduced levels of MCM2-7 have fewer dormant origins, are cancer-prone and are genetically unstable, demonstrating the importance of dormant origins for preserving genome integrity. We review the function of dormant origins, the molecular mechanism of their regulation and their physiological implications.

    AB - Many replication origins that are licensed by loading MCM2-7 complexes in G1 are not normally used. Activation of these dormant origins during S phase provides a first line of defence for the genome if replication is inhibited. When replication forks fail, dormant origins are activated within regions of the genome currently engaged in replication. At the same time, DNA damage-response kinases activated by the stalled forks preferentially suppress the assembly of new replication factories, thereby ensuring that chromosomal regions experiencing replicative stress complete synthesis before new regions of the genome are replicated. Mice expressing reduced levels of MCM2-7 have fewer dormant origins, are cancer-prone and are genetically unstable, demonstrating the importance of dormant origins for preserving genome integrity. We review the function of dormant origins, the molecular mechanism of their regulation and their physiological implications.

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    KW - XENOPUS EGG EXTRACTS

    KW - HUMAN-CELLS

    KW - S-PHASE

    KW - MCM PROTEINS

    KW - CHECKPOINT RESPONSES

    KW - FACTORY ACTIVATION

    KW - ULTRAVIOLET-LIGHT

    KW - TUMOR SUPPRESSION

    KW - LICENSING SYSTEM

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    DO - 10.1016/j.tibs.2011.05.002

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    JO - Trends in Biochemical Sciences

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