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論文題目
Ectopic expression of meiotic cohesin generates chromosomeinstability in cancer cell line
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作者
Abdelhalim Boukaba, Jian Liu, Carl Ward, Qiongfang Wu, Alexei Arnaoutov, Jierong Liang, Elena M Pugacheva, Mary Dasso, Victor Lobanenkov, Miguel Esteban, Alexander V Strunnikov
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論文出處
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刊物名稱
Proceedings of the National Academy of Sciences of the United States of America
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年卷期頁
2022, 119, 40, e2204071119
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聯(lián)系作者
Alexander V Strunnikov
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影響因子
12.779
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摘要
Many tumors express meiotic genes that could potentially drive somatic chromosome instability. While germline cohesin subunits SMC1B, STAG3, and REC8 are widely expressed in many cancers, messenger RNA and protein for RAD21L subunit are expressed at very low levels. To elucidate the potential of meiotic cohesins to contribute to genome instability, their expression was investigated in human cell lines, predominately in DLD-1. While the induction of the REC8 complex resulted in a mild mitotic phenotype, the expression of the RAD21L complex produced an arrested but viable cell pool, thus providing a source of DNA damage, mitotic chromosome missegregation, sporadic polyteny, and altered gene expression. We also found that genomic binding profiles of ectopically expressed meiotic cohesin complexes were reminiscent of their corresponding specific binding patterns in testis. Furthermore, meiotic cohesins were found to localize to the same sites as BORIS/CTCFL, rather than CTCF sites normally associated with the somatic cohesin complex. These findings highlight the existence of a germline epigenomic memory that is conserved in cells that normally do not express meiotic genes. Our results reveal a mechanism of action by unduly expressed meiotic cohesins that potentially links them to aneuploidy and chromosomal mutations in affected cells.
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英文摘要
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