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Hind Ghezraoui - One of the best experts on this subject based on the ideXlab platform.

  • 53BP1 cooperation with the REV7–shieldin complex underpins DNA Structure-specific NHEJ
    Nature, 2018
    Co-Authors: Hind Ghezraoui, Catarina Oliveira, Jordan R. Becker, Kirstin Bilham, Daniela Moralli, Consuelo Anzilotti, Roman Fischer, Mukta Deobagkar-lele, Maria Sanchiz-calvo, Elena Fueyo-marcos
    Abstract:

    The specificity of 53BP1 and its co-factors for particular DNA substrates during non-homologous end joining (NHEJ) derives from REV7–shieldin, a four-subunit DNA-binding complex that is required for REV7-dependent NHEJ but not for REV7-dependent DNA interstrand cross-link repair. 53BP1 governs a specialized, context-specific branch of the classical non-homologous end joining DNA double-strand break repair pathway. Mice lacking 53bp1 (also known as Trp53bp1 ) are immunodeficient owing to a complete loss of immunoglobulin class-switch recombination^ 1 , 2 , and reduced fidelity of long-range V(D)J recombination^ 3 . The 53BP1-dependent pathway is also responsible for pathological joining events at dysfunctional telomeres^ 4 , and its unrestricted activity in Brca1- deficient cellular and tumour models causes genomic instability and oncogenesis^ 5 – 7 . Cells that lack core non-homologous end joining proteins are profoundly radiosensitive^ 8 , unlike 53BP1-deficient cells^ 9 , 10 , which suggests that 53BP1 and its co-factors act on specific DNA substrates. Here we show that 53BP1 cooperates with its downstream effector protein REV7 to promote non-homologous end joining during class-switch recombination, but REV7 is not required for 53BP1-dependent V(D)J recombination. We identify shieldin—a four-subunit putative single-stranded DNA-binding complex comprising REV7, c20orf196 (SHLD1), FAM35A (SHLD2) and FLJ26957 (SHLD3)—as the factor that explains this specificity. Shieldin is essential for REV7-dependent DNA end-protection and non-homologous end joining during class-switch recombination, and supports toxic non-homologous end joining in Brca1- deficient cells, yet is dispensable for REV7-dependent interstrand cross-link repair. The 53BP1 pathway therefore comprises distinct double-strand break repair activities within chromatin and single-stranded DNA compartments, which explains both the immunological differences between 53bp1- and Rev7- deficient mice and the context specificity of the pathway.

  • 53bp1 cooperation with the rev7 shieldin complex underpins DNA Structure specific nhej
    Nature, 2018
    Co-Authors: Hind Ghezraoui, Catarina Oliveira, Jordan R. Becker, Kirstin Bilham, Daniela Moralli, Consuelo Anzilotti, Roman Fischer, Mukta Deobagkarlele, Maria Sanchizcalvo, Elena Fueyomarcos
    Abstract:

    53BP1 governs a specialized, context-specific branch of the classical non-homologous end joining DNA double-strand break repair pathway. Mice lacking 53bp1 (also known as Trp53bp1) are immunodeficient owing to a complete loss of immunoglobulin class-switch recombination1,2, and reduced fidelity of long-range V(D)J recombination3. The 53BP1-dependent pathway is also responsible for pathological joining events at dysfunctional telomeres4, and its unrestricted activity in Brca1-deficient cellular and tumour models causes genomic instability and oncogenesis5–7. Cells that lack core non-homologous end joining proteins are profoundly radiosensitive8, unlike 53BP1-deficient cells9,10, which suggests that 53BP1 and its co-factors act on specific DNA substrates. Here we show that 53BP1 cooperates with its downstream effector protein REV7 to promote non-homologous end joining during class-switch recombination, but REV7 is not required for 53BP1-dependent V(D)J recombination. We identify shieldin—a four-subunit putative single-stranded DNA-binding complex comprising REV7, c20orf196 (SHLD1), FAM35A (SHLD2) and FLJ26957 (SHLD3)—as the factor that explains this specificity. Shieldin is essential for REV7-dependent DNA end-protection and non-homologous end joining during class-switch recombination, and supports toxic non-homologous end joining in Brca1-deficient cells, yet is dispensable for REV7-dependent interstrand cross-link repair. The 53BP1 pathway therefore comprises distinct double-strand break repair activities within chromatin and single-stranded DNA compartments, which explains both the immunological differences between 53bp1- and Rev7- deficient mice and the context specificity of the pathway.

Elena Fueyo-marcos - One of the best experts on this subject based on the ideXlab platform.

  • 53BP1 cooperation with the REV7–shieldin complex underpins DNA Structure-specific NHEJ
    Nature, 2018
    Co-Authors: Hind Ghezraoui, Catarina Oliveira, Jordan R. Becker, Kirstin Bilham, Daniela Moralli, Consuelo Anzilotti, Roman Fischer, Mukta Deobagkar-lele, Maria Sanchiz-calvo, Elena Fueyo-marcos
    Abstract:

    The specificity of 53BP1 and its co-factors for particular DNA substrates during non-homologous end joining (NHEJ) derives from REV7–shieldin, a four-subunit DNA-binding complex that is required for REV7-dependent NHEJ but not for REV7-dependent DNA interstrand cross-link repair. 53BP1 governs a specialized, context-specific branch of the classical non-homologous end joining DNA double-strand break repair pathway. Mice lacking 53bp1 (also known as Trp53bp1 ) are immunodeficient owing to a complete loss of immunoglobulin class-switch recombination^ 1 , 2 , and reduced fidelity of long-range V(D)J recombination^ 3 . The 53BP1-dependent pathway is also responsible for pathological joining events at dysfunctional telomeres^ 4 , and its unrestricted activity in Brca1- deficient cellular and tumour models causes genomic instability and oncogenesis^ 5 – 7 . Cells that lack core non-homologous end joining proteins are profoundly radiosensitive^ 8 , unlike 53BP1-deficient cells^ 9 , 10 , which suggests that 53BP1 and its co-factors act on specific DNA substrates. Here we show that 53BP1 cooperates with its downstream effector protein REV7 to promote non-homologous end joining during class-switch recombination, but REV7 is not required for 53BP1-dependent V(D)J recombination. We identify shieldin—a four-subunit putative single-stranded DNA-binding complex comprising REV7, c20orf196 (SHLD1), FAM35A (SHLD2) and FLJ26957 (SHLD3)—as the factor that explains this specificity. Shieldin is essential for REV7-dependent DNA end-protection and non-homologous end joining during class-switch recombination, and supports toxic non-homologous end joining in Brca1- deficient cells, yet is dispensable for REV7-dependent interstrand cross-link repair. The 53BP1 pathway therefore comprises distinct double-strand break repair activities within chromatin and single-stranded DNA compartments, which explains both the immunological differences between 53bp1- and Rev7- deficient mice and the context specificity of the pathway.

Elena Fueyomarcos - One of the best experts on this subject based on the ideXlab platform.

  • 53bp1 cooperation with the rev7 shieldin complex underpins DNA Structure specific nhej
    Nature, 2018
    Co-Authors: Hind Ghezraoui, Catarina Oliveira, Jordan R. Becker, Kirstin Bilham, Daniela Moralli, Consuelo Anzilotti, Roman Fischer, Mukta Deobagkarlele, Maria Sanchizcalvo, Elena Fueyomarcos
    Abstract:

    53BP1 governs a specialized, context-specific branch of the classical non-homologous end joining DNA double-strand break repair pathway. Mice lacking 53bp1 (also known as Trp53bp1) are immunodeficient owing to a complete loss of immunoglobulin class-switch recombination1,2, and reduced fidelity of long-range V(D)J recombination3. The 53BP1-dependent pathway is also responsible for pathological joining events at dysfunctional telomeres4, and its unrestricted activity in Brca1-deficient cellular and tumour models causes genomic instability and oncogenesis5–7. Cells that lack core non-homologous end joining proteins are profoundly radiosensitive8, unlike 53BP1-deficient cells9,10, which suggests that 53BP1 and its co-factors act on specific DNA substrates. Here we show that 53BP1 cooperates with its downstream effector protein REV7 to promote non-homologous end joining during class-switch recombination, but REV7 is not required for 53BP1-dependent V(D)J recombination. We identify shieldin—a four-subunit putative single-stranded DNA-binding complex comprising REV7, c20orf196 (SHLD1), FAM35A (SHLD2) and FLJ26957 (SHLD3)—as the factor that explains this specificity. Shieldin is essential for REV7-dependent DNA end-protection and non-homologous end joining during class-switch recombination, and supports toxic non-homologous end joining in Brca1-deficient cells, yet is dispensable for REV7-dependent interstrand cross-link repair. The 53BP1 pathway therefore comprises distinct double-strand break repair activities within chromatin and single-stranded DNA compartments, which explains both the immunological differences between 53bp1- and Rev7- deficient mice and the context specificity of the pathway.

Consuelo Anzilotti - One of the best experts on this subject based on the ideXlab platform.

  • 53BP1 cooperation with the REV7–shieldin complex underpins DNA Structure-specific NHEJ
    Nature, 2018
    Co-Authors: Hind Ghezraoui, Catarina Oliveira, Jordan R. Becker, Kirstin Bilham, Daniela Moralli, Consuelo Anzilotti, Roman Fischer, Mukta Deobagkar-lele, Maria Sanchiz-calvo, Elena Fueyo-marcos
    Abstract:

    The specificity of 53BP1 and its co-factors for particular DNA substrates during non-homologous end joining (NHEJ) derives from REV7–shieldin, a four-subunit DNA-binding complex that is required for REV7-dependent NHEJ but not for REV7-dependent DNA interstrand cross-link repair. 53BP1 governs a specialized, context-specific branch of the classical non-homologous end joining DNA double-strand break repair pathway. Mice lacking 53bp1 (also known as Trp53bp1 ) are immunodeficient owing to a complete loss of immunoglobulin class-switch recombination^ 1 , 2 , and reduced fidelity of long-range V(D)J recombination^ 3 . The 53BP1-dependent pathway is also responsible for pathological joining events at dysfunctional telomeres^ 4 , and its unrestricted activity in Brca1- deficient cellular and tumour models causes genomic instability and oncogenesis^ 5 – 7 . Cells that lack core non-homologous end joining proteins are profoundly radiosensitive^ 8 , unlike 53BP1-deficient cells^ 9 , 10 , which suggests that 53BP1 and its co-factors act on specific DNA substrates. Here we show that 53BP1 cooperates with its downstream effector protein REV7 to promote non-homologous end joining during class-switch recombination, but REV7 is not required for 53BP1-dependent V(D)J recombination. We identify shieldin—a four-subunit putative single-stranded DNA-binding complex comprising REV7, c20orf196 (SHLD1), FAM35A (SHLD2) and FLJ26957 (SHLD3)—as the factor that explains this specificity. Shieldin is essential for REV7-dependent DNA end-protection and non-homologous end joining during class-switch recombination, and supports toxic non-homologous end joining in Brca1- deficient cells, yet is dispensable for REV7-dependent interstrand cross-link repair. The 53BP1 pathway therefore comprises distinct double-strand break repair activities within chromatin and single-stranded DNA compartments, which explains both the immunological differences between 53bp1- and Rev7- deficient mice and the context specificity of the pathway.

  • 53bp1 cooperation with the rev7 shieldin complex underpins DNA Structure specific nhej
    Nature, 2018
    Co-Authors: Hind Ghezraoui, Catarina Oliveira, Jordan R. Becker, Kirstin Bilham, Daniela Moralli, Consuelo Anzilotti, Roman Fischer, Mukta Deobagkarlele, Maria Sanchizcalvo, Elena Fueyomarcos
    Abstract:

    53BP1 governs a specialized, context-specific branch of the classical non-homologous end joining DNA double-strand break repair pathway. Mice lacking 53bp1 (also known as Trp53bp1) are immunodeficient owing to a complete loss of immunoglobulin class-switch recombination1,2, and reduced fidelity of long-range V(D)J recombination3. The 53BP1-dependent pathway is also responsible for pathological joining events at dysfunctional telomeres4, and its unrestricted activity in Brca1-deficient cellular and tumour models causes genomic instability and oncogenesis5–7. Cells that lack core non-homologous end joining proteins are profoundly radiosensitive8, unlike 53BP1-deficient cells9,10, which suggests that 53BP1 and its co-factors act on specific DNA substrates. Here we show that 53BP1 cooperates with its downstream effector protein REV7 to promote non-homologous end joining during class-switch recombination, but REV7 is not required for 53BP1-dependent V(D)J recombination. We identify shieldin—a four-subunit putative single-stranded DNA-binding complex comprising REV7, c20orf196 (SHLD1), FAM35A (SHLD2) and FLJ26957 (SHLD3)—as the factor that explains this specificity. Shieldin is essential for REV7-dependent DNA end-protection and non-homologous end joining during class-switch recombination, and supports toxic non-homologous end joining in Brca1-deficient cells, yet is dispensable for REV7-dependent interstrand cross-link repair. The 53BP1 pathway therefore comprises distinct double-strand break repair activities within chromatin and single-stranded DNA compartments, which explains both the immunological differences between 53bp1- and Rev7- deficient mice and the context specificity of the pathway.

Catarina Oliveira - One of the best experts on this subject based on the ideXlab platform.

  • 53BP1 cooperation with the REV7–shieldin complex underpins DNA Structure-specific NHEJ
    Nature, 2018
    Co-Authors: Hind Ghezraoui, Catarina Oliveira, Jordan R. Becker, Kirstin Bilham, Daniela Moralli, Consuelo Anzilotti, Roman Fischer, Mukta Deobagkar-lele, Maria Sanchiz-calvo, Elena Fueyo-marcos
    Abstract:

    The specificity of 53BP1 and its co-factors for particular DNA substrates during non-homologous end joining (NHEJ) derives from REV7–shieldin, a four-subunit DNA-binding complex that is required for REV7-dependent NHEJ but not for REV7-dependent DNA interstrand cross-link repair. 53BP1 governs a specialized, context-specific branch of the classical non-homologous end joining DNA double-strand break repair pathway. Mice lacking 53bp1 (also known as Trp53bp1 ) are immunodeficient owing to a complete loss of immunoglobulin class-switch recombination^ 1 , 2 , and reduced fidelity of long-range V(D)J recombination^ 3 . The 53BP1-dependent pathway is also responsible for pathological joining events at dysfunctional telomeres^ 4 , and its unrestricted activity in Brca1- deficient cellular and tumour models causes genomic instability and oncogenesis^ 5 – 7 . Cells that lack core non-homologous end joining proteins are profoundly radiosensitive^ 8 , unlike 53BP1-deficient cells^ 9 , 10 , which suggests that 53BP1 and its co-factors act on specific DNA substrates. Here we show that 53BP1 cooperates with its downstream effector protein REV7 to promote non-homologous end joining during class-switch recombination, but REV7 is not required for 53BP1-dependent V(D)J recombination. We identify shieldin—a four-subunit putative single-stranded DNA-binding complex comprising REV7, c20orf196 (SHLD1), FAM35A (SHLD2) and FLJ26957 (SHLD3)—as the factor that explains this specificity. Shieldin is essential for REV7-dependent DNA end-protection and non-homologous end joining during class-switch recombination, and supports toxic non-homologous end joining in Brca1- deficient cells, yet is dispensable for REV7-dependent interstrand cross-link repair. The 53BP1 pathway therefore comprises distinct double-strand break repair activities within chromatin and single-stranded DNA compartments, which explains both the immunological differences between 53bp1- and Rev7- deficient mice and the context specificity of the pathway.

  • 53bp1 cooperation with the rev7 shieldin complex underpins DNA Structure specific nhej
    Nature, 2018
    Co-Authors: Hind Ghezraoui, Catarina Oliveira, Jordan R. Becker, Kirstin Bilham, Daniela Moralli, Consuelo Anzilotti, Roman Fischer, Mukta Deobagkarlele, Maria Sanchizcalvo, Elena Fueyomarcos
    Abstract:

    53BP1 governs a specialized, context-specific branch of the classical non-homologous end joining DNA double-strand break repair pathway. Mice lacking 53bp1 (also known as Trp53bp1) are immunodeficient owing to a complete loss of immunoglobulin class-switch recombination1,2, and reduced fidelity of long-range V(D)J recombination3. The 53BP1-dependent pathway is also responsible for pathological joining events at dysfunctional telomeres4, and its unrestricted activity in Brca1-deficient cellular and tumour models causes genomic instability and oncogenesis5–7. Cells that lack core non-homologous end joining proteins are profoundly radiosensitive8, unlike 53BP1-deficient cells9,10, which suggests that 53BP1 and its co-factors act on specific DNA substrates. Here we show that 53BP1 cooperates with its downstream effector protein REV7 to promote non-homologous end joining during class-switch recombination, but REV7 is not required for 53BP1-dependent V(D)J recombination. We identify shieldin—a four-subunit putative single-stranded DNA-binding complex comprising REV7, c20orf196 (SHLD1), FAM35A (SHLD2) and FLJ26957 (SHLD3)—as the factor that explains this specificity. Shieldin is essential for REV7-dependent DNA end-protection and non-homologous end joining during class-switch recombination, and supports toxic non-homologous end joining in Brca1-deficient cells, yet is dispensable for REV7-dependent interstrand cross-link repair. The 53BP1 pathway therefore comprises distinct double-strand break repair activities within chromatin and single-stranded DNA compartments, which explains both the immunological differences between 53bp1- and Rev7- deficient mice and the context specificity of the pathway.