Journal
NATURE STRUCTURAL & MOLECULAR BIOLOGY
Volume 23, Issue 6, Pages 522-530Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.3211
Keywords
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Funding
- Basser Center for BRCA
- US National Institutes of Health [R01CA142776, R01CA190415, P50CA083638, P50CA174523, R01CA148759, R01NS094533]
- Breast Cancer Alliance
- Ovarian Cancer Research Fund
- Foundation for Women's Cancer
- Marsha Rivkin Center for Ovarian Cancer Research
- China Scholarship Council
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Long noncoding RNAs (IncRNAs) play critical roles during tumorigenesis by functioning as scaffolds that regulate protein protein, protein-DNA or protein-RNA interactions. Using a clinically guided genetic screening approach, we identified IncRNA in nonhomologous end joining (NHEJ) pathway 1 (LINP1), which is overexpressed in human triple-negative breast cancer. We found that LINP1 enhances repair of DNA double-strand breaks by serving as a scaffold linking Ku80 and DNA-PKcs, thereby coordinating the NHEJ pathway. Importantly, blocking LINP1, which is regulated by p53 and epidermal growth factor receptor (EGFR) signaling, increases the sensitivity of the tumor-cell response to radiotherapy in breast cancer.
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