越来越多的研究表明转录因子参与了DNA损伤应答和基因组稳定性维持，但是相关的分子机理并不清楚。BEND3作为一个转录因子，能够与染色质重塑复合物NuRD结合并抑制转录。由于NuRD复合物在DNA损伤修复过程中扮演着重要角色，我们推测BEND3可能协同NuRD维持基因组稳定性。我们的初步研究表明，BEND3可以被招募到DNA损伤区域，其功能缺失显著的抑制了细胞同源重组修复能力；且BEND3与损伤应答复合物MRN存在相互作用，可能参与了DNA末端剪切。以上结果初步支持了我们的假说。后续研究中，我们将致力于探索BEND3在特征性染色质环境下，如何协同NuRD调控MRN复合物和DNA双链损伤应答，以及BEND3表达异常在乳腺癌基因组不稳定性中的作用。该研究将有助于认识转录因子/染色质重塑复合物调节DNA损伤应答修复和基因组稳定性维持的分子机理，并为肿瘤等疾病的靶向治疗提供一定的指导。

Emerging evidence suggests that multiple transcription factors have been involve in DNA damage response (DDR). However, the molecular mechanism of how transcription factors contribute to response and repair of DNA damage remains unclear. BEND3, originally known as KIAA1553, is a transcription factor containing four BEN domains, and it has been implicated in heterochromatin formation and transcription inhibition through interacting with the nucleosome remodeling and deacetylase (NuRD) complex. Since NuRD complex plays a critical role in DDR, we propose that BEND3 is a potential regulator of genome integrity. Our preliminary data suggested that BEND3 is physically associated with the MRE11-RAD50-NBS1 (MRN) complex, a conserved and essential DDR factor that controls DNA double-strand break (DSB) repair, DNA end resection and checkpoint signaling. Importantly, we demonstrated that DsRed-tagged BEND3 was recruited to damaged sites rapidly after laser micro-irradiation, manifested by fast accumulation of DsRed signal around the break sites, and BEND3 depletion profoundly inhibits the efficiency of homologous recombination (HR), but not non-homologous end joining (NHEJ) repair of DSBs. Bioinformatics analysis indicated that BEND3 is highly expressed in multiple tumors including breast cancer and highly expressed BEND3 is associated with worse survivals of breast cancer patients. We also showed that BEND3 is required for breast cancer cells to desensitize DNA damage. These results indicated that BEND3 is an important player in maintenance of genome stability and its dysregulation may contribute to genome instability of breast cancer. However, it remains to be investigated that how BEND3 coordinates with the MRN and NuRD complex to regulate the response and repair of DSBs in specific chromatin regions. Also, it will be interesting to explore how BEND3-promoted DSB repair contributes to tumor-associated genome instability and breast carcinogenesis. We envision that the further understanding of the molecular mechanisms through which BEND3 operates in DSB repair, in combination with the elucidation of the physiological interactions between chromatin remodeling complex and different DSB repair pathways, will guide new approaches development to sustain genome stability and provide therapeutic opportunities for many human diseases including cancer and premature aging.