Abstract | BACKGROUND AND AIM: METHODS: Immunohistochemistry was carried out to determine TCOF1 expression in GC tissues. Immunofluorescence, co-IP, and DNA fiber assays were conducted to investigate the function of TCOF1 in GC-derived BGC-823 and SGC-7901 cell lines. RESULTS: TCOF1 expression was aberrantly increased in GC tissues compared with adjacent normal tissues. In addition, we found that TCOF1 left the nucleolus and localized to R-loops ( DNA/ RNA hybrids) during S phase in GC cells. Furthermore, TCOF1 interacted with DDX5 and suppressed R-loop levels. Knockdown of TCOF1 led to increased nucleoplasmic R-loops specifically during S phase, which restrained DNA replication and cell proliferation. Overexpression of R-loop eraser RNaseH1 rescued the DNA synthesis defects and decreased DNA damage caused by TCOF1 depletion. CONCLUSION: These findings demonstrate a novel role of TCOF1 in maintaining GC cell proliferation by alleviating R-loop associated DNA replication stress.
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Authors | Xin Nie, Chong Zhao, Yuan Zhang, Wenqi Huang, Youlian Zhou, Haiying Liu, Yuqiang Nie, Keping Xie, Lin Jia |
Journal | Journal of gastroenterology and hepatology
(J Gastroenterol Hepatol)
Vol. 38
Issue 7
Pg. 1170-1180
(Jul 2023)
ISSN: 1440-1746 [Electronic] Australia |
PMID | 36941105
(Publication Type: Journal Article)
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Copyright | © 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd. |
Chemical References |
- Phosphoproteins
- Nuclear Proteins
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Topics |
- Humans
- R-Loop Structures
- Phosphoproteins
(genetics)
- Nuclear Proteins
(genetics, metabolism)
- Stomach Neoplasms
(genetics)
- DNA Replication
- Cell Proliferation
(genetics)
- Ribosomes
(metabolism)
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