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The genomic stability regulator PTIP is required for proper chromosome segregation in mitosis
2022-09-24
发表期刊CELL DIVISION (IF:2.8[JCR-2023],3.1[5-Year])
EISSN1747-1028
卷号17期号:1
发表状态已发表
DOI10.1186/s13008-022-00081-4
摘要Background: 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. 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. Conclusion: 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.
关键词Centrosome Chromosome segregation DNA damage Genetic instability Mitosis PTIP
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收录类别SCIE
语种英语
Scopus 记录号2-s2.0-85138740752
来源库Scopus
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文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/238183
专题生命科学与技术学院_博士生
免疫化学研究所
国际事务处
通讯作者Kang, Jungseog
作者单位
1.Arts and Science,New York University Shanghai,Shanghai,200122,China
2.Shanghai Institute for Advanced Immunochemical Studies,ShanghaiTech University,Shanghai,201210,China
3.NYU-ECNU Center for Computational Chemistry at NYU Shanghai,Shanghai,200062,China
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GB/T 7714
Zhang, Fengxia,Wei, Mingxuan,Chen, Haoran,et al. The genomic stability regulator PTIP is required for proper chromosome segregation in mitosis[J]. CELL DIVISION,2022,17(1).
APA Zhang, Fengxia,Wei, Mingxuan,Chen, Haoran,Ji, Liting,Nie, Yan,&Kang, Jungseog.(2022).The genomic stability regulator PTIP is required for proper chromosome segregation in mitosis.CELL DIVISION,17(1).
MLA Zhang, Fengxia,et al."The genomic stability regulator PTIP is required for proper chromosome segregation in mitosis".CELL DIVISION 17.1(2022).
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