The genomic stability regulator PTIP is required for proper chromosome segregation in mitosis.
The genomic stability regulator PTIP is required for proper chromosome segregation in mitosis.
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有丝分裂中正确的染色体分离需要基因组稳定性调节剂 PTIP
DOI：
10.1186/s13008-022-00081-4
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发表时间：
2022-09-24
期刊：
影响因子：
2.3
通讯作者：
Kang, Jungseog
中科院分区：
文献类型：
--
作者：
Zhang, Fengxia;Wei, Mingxuan;Chen, Haoran;Ji, Liting;Nie, Yan;Kang, Jungseog
Pax转录激活结构域相互作用蛋白（PTIP）是一种核蛋白，是血管、肾脏、B细胞和脂肪细胞发育中H3K4甲基化基因激活的重要组成部分。此外，它在高等真核细胞的基因组稳定性中起着关键作用。它与53BP1结合，并对抗不适当的同源重组，以获得适当的DNA损伤反应。有趣的是，一项早期研究报道了PTIP失活后有丝分裂缺陷，但不清楚PTIP是否直接促进有丝分裂过程。在这里，我们发现PTIP对于HeLa细胞的有丝分裂完整性至关重要。PTIP失活增加有丝分裂退出期间的细胞死亡，这似乎是由有丝分裂直接缺陷引起的。在脚泊苷治疗的间期，PTIP失活不影响G2M DNA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、染色体排列效率低下和细胞死亡增加。此外，PTIP通过c端BRCT结构域定位于有丝分裂中心体。该研究揭示了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，在各种肿瘤中发生的它的失调，可能会通过引入异常的DNA损伤反应以及错误的染色体分离来破坏基因组的稳定。在线版本包含补充资料，下载地址：10.1186/s13008-022-00081-4。
The Pax transcription activation domain-interacting protein (PTIP) is a nuclear protein that is an essential component of H3K4 methylation for gene activation in vascular, kidney, B cell, and adipocyte development. Furthermore, it plays a key role in genomic stability in higher eukaryotic cells. It binds to 53BP1 and antagonizes inappropriate homologous recombination for a proper DNA damage response. Interestingly, an early study reported mitotic defects after PTIP inactivation, but it is not clear whether PTIP directly facilitates mitotic processes. 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. 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. The online version contains supplementary material available at 10.1186/s13008-022-00081-4.
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