1. A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer.

    Cell 162(1):146 (2015) PMID 26140595

    KRAS is one of the most frequently mutated oncogenes in human cancer. Despite substantial efforts, no clinically applicable strategy has yet been developed to effectively treat KRAS-mutant tumors. Here, we perform a cell-line-based screen and identify strong synergistic interactions between cell...
  2. REV7 counteracts DNA double-strand break resection and affects PARP inhibition.

    Nature 521(7553):541 (2015) PMID 25799992

    Error-free repair of DNA double-strand breaks (DSBs) is achieved by homologous recombination (HR), and BRCA1 is an important factor for this repair pathway. In the absence of BRCA1-mediated HR, the administration of PARP inhibitors induces synthetic lethality of tumour cells of patients with bre...
  3. Myc and Ras oncogenes engage different energy metabolism programs and evoke distinct patterns of oxidative and DNA replication stress.

    Molecular Oncology 9(3):601 (2015) PMID 25435281

    Both Myc and Ras oncogenes impact cellular metabolism, deregulate redox homeostasis and trigger DNA replication stress (RS) that compromises genomic integrity. However, how are such oncogene-induced effects evoked and temporally related, to what extent are these kinetic parameters shared by Myc ...
  4. TRIP12 and UBR5 Suppress Spreading of Chromatin Ubiquitylation at Damaged Chromosomes

    Cell 159(6):1476 (2014)

  5. TRIP12 and UBR5 Suppress Spreading of Chromatin Ubiquitylation at Damaged Chromosomes

    Cell 159(6):1476 (2014)

  6. Patterns of DNA damage response in intracranial germ cell tumors versus glioblastomas reflect cell of origin rather than brain environment: implications for the anti-tumor barrier concept and treatment.

    Molecular Oncology 8(8):1667 (2014) PMID 25066726

    The DNA damage response (DDR) machinery becomes commonly activated in response to oncogenes and during early stages of development of solid malignancies, with an exception of testicular germ cell tumors (TGCTs). The active DDR signaling evokes cell death or senescence but this anti-tumor barrier...
  7. Patterns of DNA damage response in intracranial germ cell tumors versus glioblastomas reflect cell of origin rather than brain environment: Implications for the anti-tumor barrier concept and treatment

    Molecular Oncology 8(8):1667 (2014)

    The DNA damage response (DDR) machinery becomes commonly activated in response to oncogenes and during early stages of development of solid malignancies, with an exception of testicular germ cell tumors (TGCTs). The active DDR signaling evokes cell death or senescence but this anti-tum...
  8. Patterns of DNA damage response in intracranial germ cell tumors versus glioblastomas reflect cell of origin rather than brain environment: Implications for the anti-tumor barrier concept and treatment.

    Molecular Oncology 8(8):1667 (2014) PMID 25066726

    The DNA damage response (DDR) machinery becomes commonly activated in response to oncogenes and during early stages of development of solid malignancies, with an exception of testicular germ cell tumors (TGCTs). The active DDR signaling evokes cell death or senescence but this anti-tumor barrier...
  9. A short acidic motif in ARF guards against mitochondrial dysfunction and melanoma susceptibility.

    Nature Communications 5:5348 (2014) PMID 25370744

    ARF is a small, highly basic protein that can be induced by oncogenic stimuli and exerts growth-inhibitory and tumour-suppressive activities through the activation of p53. Here we show that, in human melanocytes, ARF is cytoplasmic, constitutively expressed, and required for maintaining low stea...
  10. A short acidic motif in ARF guards against mitochondrial dysfunction and melanoma susceptibility.

    Nature Communications 5:5348 (2014) PMID 25370744

    ARF is a small, highly basic protein that can be induced by oncogenic stimuli and exerts growth-inhibitory and tumour-suppressive activities through the activation of p53. Here we show that, in human melanocytes, ARF is cytoplasmic, constitutively expressed, and required for maintaining low stea...
  11. A short acidic motif in ARF guards against mitochondrial dysfunction and melanoma susceptibility.

    Nature Communications 5:5348 (2014) PMID 25370744

    ARF is a small, highly basic protein that can be induced by oncogenic stimuli and exerts growth-inhibitory and tumour-suppressive activities through the activation of p53. Here we show that, in human melanocytes, ARF is cytoplasmic, constitutively expressed, and required for maintaining low stea...
  12. JMJD1C demethylates MDC1 to regulate the RNF8 and BRCA1-mediated chromatin response to DNA breaks.

    Nature Structural & Molecular Biology 20(12):1425 (2013) PMID 24240613

    Chromatin ubiquitylation flanking DNA double-strand breaks (DSBs), mediated by RNF8 and RNF168 ubiquitin ligases, orchestrates a two-branch pathway, recruiting repair factors 53BP1 or the RAP80-BRCA1 complex. We report that human demethylase JMJD1C regulates the RAP80-BRCA1 branch of this DNA-da...
  13. JMJD1C demethylates MDC1 to regulate the RNF8 and BRCA1-mediated chromatin response to DNA breaks.

    Nature Structural & Molecular Biology 20(12):1425 (2013) PMID 24240613

    Chromatin ubiquitylation flanking DNA double-strand breaks (DSBs), mediated by RNF8 and RNF168 ubiquitin ligases, orchestrates a two-branch pathway, recruiting repair factors 53BP1 or the RAP80-BRCA1 complex. We report that human demethylase JMJD1C regulates the RAP80-BRCA1 branch of this DNA-da...
  14. Androgen receptor signaling fuels DNA repair and radioresistance in prostate cancer.

    Cancer Discovery 3(11):1222 (2013) PMID 24203954

    Successful treatment by genotoxic modalities including radiotherapy is commonly hampered by treatment resistance in advanced cancers. Two new studies now reveal that androgen receptor signaling transcriptionally upregulates a large subset of DNA repair genes, thereby enhancing the repair capacit...
  15. Androgen receptor signaling fuels DNA repair and radioresistance in prostate cancer.

    Cancer Discovery 3(11):1222 (2013) PMID 24203954

    Successful treatment by genotoxic modalities including radiotherapy is commonly hampered by treatment resistance in advanced cancers. Two new studies now reveal that androgen receptor signaling transcriptionally upregulates a large subset of DNA repair genes, thereby enhancing the repair capacit...
  16. Functional interplay between the DNA-damage-response kinase ATM and ARF tumour suppressor protein in human cancer.

    Nature Cell Biology 15(8):967 (2013) PMID 23851489

    The DNA damage response (DDR) pathway and ARF function as barriers to cancer development. Although commonly regarded as operating independently of each other, some studies proposed that ARF is positively regulated by the DDR. Contrary to either scenario, we found that in human oncogene-transform...
  17. Functional interplay between the DNA-damage-response kinase ATM and ARF tumour suppressor protein in human cancer.

    Nature Cell Biology 15(8):967 (2013) PMID 23851489

    The DNA damage response (DDR) pathway and ARF function as barriers to cancer development. Although commonly regarded as operating independently of each other, some studies proposed that ARF is positively regulated by the DDR. Contrary to either scenario, we found that in human oncogene-transform...
  18. Functional interplay between the DNA-damage-response kinase ATM and ARF tumour suppressor protein in human cancer.

    Nature Cell Biology 15(8):967 (2013) PMID 23851489

    The DNA damage response (DDR) pathway and ARF function as barriers to cancer development. Although commonly regarded as operating independently of each other, some studies proposed that ARF is positively regulated by the DDR. Contrary to either scenario, we found that in human oncogene-transform...
  19. Myc and Ras oncogenes engage different energy metabolism programs and evoke distinct patterns of oxidative and DNA replication stress

    Molecular Oncology (2013)

    Both Myc and Ras oncogenes impact cellular metabolism, deregulate redox homeostasis and trigger DNA replication stress (RS) that compromises genomic integrity. However, how are such oncogene-induced effects evoked and temporally related, to what extent are these kinetic parameters shar...
  20. Myc and Ras oncogenes engage different energy metabolism programs and evoke distinct patterns of oxidative and DNA replication stress

    Molecular Oncology 9(3) (2013) PMID 25435281

    Both Myc and Ras oncogenes impact cellular metabolism, deregulate redox homeostasis and trigger DNA replication stress (RS) that compromises genomic integrity. However, how are such oncogene-induced effects evoked and temporally related, to what extent are these kinetic parameters shar...