Bi-directional routing of DNA mismatch repair protein human exonuclease 1 to replication foci and DNA double strand breaks

Sascha Emilie Liberti, Sofie Dabros Andersen, Jing Wang, alfred May, simona Miron, Mylene Perderiset, Guido Keijzers, Finn Cilius Nielsen, Jean-Baptiste Charbonnier, Vilhelm A. Bohr, Lene J. Rasmussen

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Resumé

    Human exonuclease 1 (hEXO1) is implicated in DNA metabolism, including replication, recombination and repair, substantiated by its interactions with PCNA, DNA helicases BLM and WRN, and several DNA mismatch repair (MMR) proteins. We investigated the sub-nuclear localization of hEXO1 during S-phase progression and in response to laser-induced DNA double strand breaks (DSBs). We show that hEXO1 and PCNA co-localize in replication foci. This apparent interaction is sustained throughout S-phase. We also demonstrate that hEXO1 is rapidly recruited to DNA DSBs. We have identified a PCNA interacting protein (PIP-box) region on hEXO1 located in its COOH-terminal ((788)QIKLNELW(795)). This motif is essential for PCNA binding and co-localization during S-phase. Recruitment of hEXO1 to DNA DSB sites is dependent on the MMR protein hMLH1. We show that two distinct hMLH1 interaction regions of hEXO1 (residues 390-490 and 787-846) are required to direct the protein to the DNA damage site. Our results reveal that protein domains in hEXO1 in conjunction with specific protein interactions control bi-directional routing of hEXO1 between on-going DNA replication and repair processes in living cells
    OriginalsprogEngelsk
    TidsskriftD N A Repair
    Vol/bind10
    Udgave nummer1
    Sider (fra-til)73-86
    ISSN1568-7864
    DOI
    StatusUdgivet - 2011

    Citer dette

    Liberti, S. E., Andersen, S. D., Wang, J., May, A., Miron, S., Perderiset, M., ... Rasmussen, L. J. (2011). Bi-directional routing of DNA mismatch repair protein human exonuclease 1 to replication foci and DNA double strand breaks. D N A Repair, 10(1), 73-86. https://doi.org/10.1016/j.dnarep.2010.09.023
    Liberti, Sascha Emilie ; Andersen, Sofie Dabros ; Wang, Jing ; May, alfred ; Miron, simona ; Perderiset, Mylene ; Keijzers, Guido ; Nielsen, Finn Cilius ; Charbonnier, Jean-Baptiste ; Bohr, Vilhelm A. ; Rasmussen, Lene J. / Bi-directional routing of DNA mismatch repair protein human exonuclease 1 to replication foci and DNA double strand breaks. I: D N A Repair. 2011 ; Bind 10, Nr. 1. s. 73-86.
    @article{01cd3289465b4cd78fd3c482570b7128,
    title = "Bi-directional routing of DNA mismatch repair protein human exonuclease 1 to replication foci and DNA double strand breaks",
    abstract = "Human exonuclease 1 (hEXO1) is implicated in DNA metabolism, including replication, recombination and repair, substantiated by its interactions with PCNA, DNA helicases BLM and WRN, and several DNA mismatch repair (MMR) proteins. We investigated the sub-nuclear localization of hEXO1 during S-phase progression and in response to laser-induced DNA double strand breaks (DSBs). We show that hEXO1 and PCNA co-localize in replication foci. This apparent interaction is sustained throughout S-phase. We also demonstrate that hEXO1 is rapidly recruited to DNA DSBs. We have identified a PCNA interacting protein (PIP-box) region on hEXO1 located in its COOH-terminal ((788)QIKLNELW(795)). This motif is essential for PCNA binding and co-localization during S-phase. Recruitment of hEXO1 to DNA DSB sites is dependent on the MMR protein hMLH1. We show that two distinct hMLH1 interaction regions of hEXO1 (residues 390-490 and 787-846) are required to direct the protein to the DNA damage site. Our results reveal that protein domains in hEXO1 in conjunction with specific protein interactions control bi-directional routing of hEXO1 between on-going DNA replication and repair processes in living cells",
    keywords = "hEXO1, PCNA, Replication foci, Double strand break, DNA mismatch repair",
    author = "Liberti, {Sascha Emilie} and Andersen, {Sofie Dabros} and Jing Wang and alfred May and simona Miron and Mylene Perderiset and Guido Keijzers and Nielsen, {Finn Cilius} and Jean-Baptiste Charbonnier and Bohr, {Vilhelm A.} and Rasmussen, {Lene J.}",
    year = "2011",
    doi = "10.1016/j.dnarep.2010.09.023",
    language = "English",
    volume = "10",
    pages = "73--86",
    journal = "D N A Repair",
    issn = "1568-7864",
    publisher = "Elsevier BV",
    number = "1",

    }

    Liberti, SE, Andersen, SD, Wang, J, May, A, Miron, S, Perderiset, M, Keijzers, G, Nielsen, FC, Charbonnier, J-B, Bohr, VA & Rasmussen, LJ 2011, 'Bi-directional routing of DNA mismatch repair protein human exonuclease 1 to replication foci and DNA double strand breaks', D N A Repair, bind 10, nr. 1, s. 73-86. https://doi.org/10.1016/j.dnarep.2010.09.023

    Bi-directional routing of DNA mismatch repair protein human exonuclease 1 to replication foci and DNA double strand breaks. / Liberti, Sascha Emilie; Andersen, Sofie Dabros; Wang, Jing; May, alfred; Miron, simona; Perderiset, Mylene; Keijzers, Guido; Nielsen, Finn Cilius; Charbonnier, Jean-Baptiste; Bohr, Vilhelm A.; Rasmussen, Lene J.

    I: D N A Repair, Bind 10, Nr. 1, 2011, s. 73-86.

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    TY - JOUR

    T1 - Bi-directional routing of DNA mismatch repair protein human exonuclease 1 to replication foci and DNA double strand breaks

    AU - Liberti, Sascha Emilie

    AU - Andersen, Sofie Dabros

    AU - Wang, Jing

    AU - May, alfred

    AU - Miron, simona

    AU - Perderiset, Mylene

    AU - Keijzers, Guido

    AU - Nielsen, Finn Cilius

    AU - Charbonnier, Jean-Baptiste

    AU - Bohr, Vilhelm A.

    AU - Rasmussen, Lene J.

    PY - 2011

    Y1 - 2011

    N2 - Human exonuclease 1 (hEXO1) is implicated in DNA metabolism, including replication, recombination and repair, substantiated by its interactions with PCNA, DNA helicases BLM and WRN, and several DNA mismatch repair (MMR) proteins. We investigated the sub-nuclear localization of hEXO1 during S-phase progression and in response to laser-induced DNA double strand breaks (DSBs). We show that hEXO1 and PCNA co-localize in replication foci. This apparent interaction is sustained throughout S-phase. We also demonstrate that hEXO1 is rapidly recruited to DNA DSBs. We have identified a PCNA interacting protein (PIP-box) region on hEXO1 located in its COOH-terminal ((788)QIKLNELW(795)). This motif is essential for PCNA binding and co-localization during S-phase. Recruitment of hEXO1 to DNA DSB sites is dependent on the MMR protein hMLH1. We show that two distinct hMLH1 interaction regions of hEXO1 (residues 390-490 and 787-846) are required to direct the protein to the DNA damage site. Our results reveal that protein domains in hEXO1 in conjunction with specific protein interactions control bi-directional routing of hEXO1 between on-going DNA replication and repair processes in living cells

    AB - Human exonuclease 1 (hEXO1) is implicated in DNA metabolism, including replication, recombination and repair, substantiated by its interactions with PCNA, DNA helicases BLM and WRN, and several DNA mismatch repair (MMR) proteins. We investigated the sub-nuclear localization of hEXO1 during S-phase progression and in response to laser-induced DNA double strand breaks (DSBs). We show that hEXO1 and PCNA co-localize in replication foci. This apparent interaction is sustained throughout S-phase. We also demonstrate that hEXO1 is rapidly recruited to DNA DSBs. We have identified a PCNA interacting protein (PIP-box) region on hEXO1 located in its COOH-terminal ((788)QIKLNELW(795)). This motif is essential for PCNA binding and co-localization during S-phase. Recruitment of hEXO1 to DNA DSB sites is dependent on the MMR protein hMLH1. We show that two distinct hMLH1 interaction regions of hEXO1 (residues 390-490 and 787-846) are required to direct the protein to the DNA damage site. Our results reveal that protein domains in hEXO1 in conjunction with specific protein interactions control bi-directional routing of hEXO1 between on-going DNA replication and repair processes in living cells

    KW - hEXO1

    KW - PCNA

    KW - Replication foci

    KW - Double strand break

    KW - DNA mismatch repair

    U2 - 10.1016/j.dnarep.2010.09.023

    DO - 10.1016/j.dnarep.2010.09.023

    M3 - Journal article

    VL - 10

    SP - 73

    EP - 86

    JO - D N A Repair

    JF - D N A Repair

    SN - 1568-7864

    IS - 1

    ER -