Scientists from Case Western Reserve University have developed a new therapeutic method to weaken and kill cancer cells. This technique could enhance the level of cancer-inhibiting protein to kill tumors by directly targeting cancer cells. This study was published in PNAS.

Prompt response to double-strand break(DSB) caused by, for example, ionization radiation(IR), requires sequential and coordinated assembly of DNA damage response(DDR) proteins at damage sites. Recent research findings reveal key roles of the tumor suppressor p53-binding protein 1(53BP1) and BRCA1 in the decision making of DSB repair.

DSB repair sits at the core of genome stability maintenance. Abnormalities in the repair pathway often lead to the development of cancers and resistance to anti-cancer therapies. Tumor suppressor p53-binding protein 1(53BP1), a protein critical in regulating DSB repair, is reduced in advanced breast tumors. Furthermore, low levels of 53BP1 correlated with poor prognosis and resistance to chemotherapy. Thus, the protein level of 53BP1 is important for therapeutic response. However, mechanisms regulating 53BP1 protein levels are poorly understood.

In this study, researchers report a previously unidentified mechanism regulating the protein level of 53BP1, specifically, ubiquitin-conjugating enzyme H7(UbcH7)-dependent ubiquitination and proteasome-dependent degradation. They further propose an innovative hypothesis that increasing the protein level of 53BP1 enhances the effect of radiotherapy or chemotherapy through suppressing faithful DSB repair.

Reference:

Han X, Zhang L, Chung J, et al. UbcH7 regulates 53BP1 stability and DSB repair[J]. Proceedings of the National Academy of Sciences, 2014, 111(49): 17456-17461.