AI Article Synopsis
- Cells respond to DNA double-strand breaks by activating repair proteins and phosphorylating histone H2AX to facilitate the repair process, highlighting the importance of various proteins like MDC1 and p53-binding protein 1.
- A novel biomarker, Bora, has been discovered to be linked to radiosensitivity, suggesting it plays a critical role in how cells react to radiation exposure.
- Downregulation of Bora enhances resistance to irradiation by speeding up the repair of double-strand breaks, influences cell cycle arrest, and interacts with MDC1, indicating its potential significance in DNA damage repair mechanisms.
Article Abstract
Following DNA double-strand breaks cells activate several DNA-damage response protein kinases, which then trigger histone H2AX phosphorylation and the accumulation of proteins such as MDC1, p53-binding protein 1, and breast cancer gene 1 at the damage site to promote DNA double-strand breaks repair. We identified a novel biomarker, Bora (previously called C13orf34), that is associated with radiosensitivity. In the current study, we set out to investigate how Bora might be involved in response to irradiation. We found a novel function of Bora in DNA damage repair response. Bora down-regulation increased colony formation in cells exposed to irradiation. This increased resistance to irradiation in Bora-deficient cells is likely due to a faster rate of double-strand breaks repair. After irradiation, Bora-knockdown cells displayed increased G2-M cell cycle arrest and increased Chk2 phosphorylation. Furthermore, Bora specifically interacted with the tandem breast cancer gene 1 C-terminal domain of MDC1 in a phosphorylation dependent manner, and overexpression of Bora could abolish irradiation induced MDC1 foci formation. In summary, Bora may play a significant role in radiosensitivity through the regulation of MDC1 and DNA repair.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351037 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0119208 | PLOS |
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