RESULTS: Here, we showed that PTIP is essential for the mitotic integrity of HeLa cells. PTIP inactivation increases cell death during mitotic exit, which appears to result from direct mitotic defects. PTIP inactivation did not affect the G2M DNA damage checkpoint during interphase upon etoposide treatment. However, in mitosis, PTIP inactivation results in prolonged mitotic time, inefficient chromosome alignment, and increased cell death. Furthermore, PTIP localizes to the mitotic centrosome via BRCT domains at the C-terminus.
CONCLUSIONS: This study reveals a novel function of PTIP in maintaining the genomic stability of higher eukaryotes during mitosis. Therefore, its deregulation, which occurs in various tumors, may destabilize the genome by introducing an abnormal DNA damage response, as well as erroneous chromosome segregation.
结果:这里,我们表明PTIP对于HeLa细胞的有丝分裂完整性至关重要。PTIP失活会增加有丝分裂退出过程中的细胞死亡,这似乎是直接有丝分裂缺陷造成的。在依托泊苷治疗的间期,PTIP失活不会影响G2MDNA损伤检查点。然而,在有丝分裂中,PTIP失活导致有丝分裂时间延长,低效的染色体排列,增加细胞死亡。此外,PTIP通过C末端的BRCT结构域定位于有丝分裂中心体。
结论:这项研究揭示了PTIP在有丝分裂过程中维持高等真核生物基因组稳定性的新功能。因此,放松管制,发生在各种肿瘤中,可能会通过引入异常的DNA损伤反应来破坏基因组的稳定性,以及错误的染色体分离。