DNA double strand breaks are the most cytotoxic lesions that can occur on the DNA. They can be repaired by different mechanisms and optimal survival requires a tight control between them. Here we uncover protein deneddylation as a major controller of repair pathway choice. Neddylation inhibition changes the normal repair profile toward an increase on homologous recombination. Indeed, RNF111/UBE2M-mediated neddylation acts as an inhibitor of BRCA1 and CtIP-mediated DNA end resection, a key process in repair pathway choice. By controlling the length of ssDNA produced during DNA resection, protein neddylation not only affects the choice between NHEJ and homologous recombination but also controls the balance between different recombination subpathways. Thus, protein neddylation status has a great impact in the way cells respond to DNA breaks.
机构:
Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Dept Med, Boston, MA 02215 USABeth Israel Deaconess Med Ctr, Div Hematol Oncol, Dept Med, Boston, MA 02215 USA
Scully, Ralph
Panday, Arvind
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Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Dept Med, Boston, MA 02215 USA
Beth Israel Deaconess Med Ctr, Canc Res Inst, Boston, MA 02215 USA
Harvard Med Sch, Boston, MA 02115 USABeth Israel Deaconess Med Ctr, Div Hematol Oncol, Dept Med, Boston, MA 02215 USA
Panday, Arvind
Elango, Rajula
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机构:
Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Dept Med, Boston, MA 02215 USA
Beth Israel Deaconess Med Ctr, Canc Res Inst, Boston, MA 02215 USA
Harvard Med Sch, Boston, MA 02115 USABeth Israel Deaconess Med Ctr, Div Hematol Oncol, Dept Med, Boston, MA 02215 USA
Elango, Rajula
Willis, Nicholas A.
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Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Dept Med, Boston, MA 02215 USABeth Israel Deaconess Med Ctr, Div Hematol Oncol, Dept Med, Boston, MA 02215 USA
机构:Mayo Clinic,Mayo Clinic Medical Scientist Training Program, Mayo Clinic Alix School of Medicine and Mayo Clinic Graduate School of Biomedical Sciences
Somaira Nowsheen
Min Deng
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机构:Mayo Clinic,Mayo Clinic Medical Scientist Training Program, Mayo Clinic Alix School of Medicine and Mayo Clinic Graduate School of Biomedical Sciences
Min Deng
Zhenkun Lou
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机构:Mayo Clinic,Mayo Clinic Medical Scientist Training Program, Mayo Clinic Alix School of Medicine and Mayo Clinic Graduate School of Biomedical Sciences