دورية أكاديمية
LINE-1 expression in cancer correlates with p53 mutation, copy number alteration, and S phase checkpoint
| العنوان: | LINE-1 expression in cancer correlates with p53 mutation, copy number alteration, and S phase checkpoint |
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| المؤلفون: | McKerrow, Wilson, Wang, Xuya, Mendez-Dorantes, Carlos, Mita, Paolo, Cao, Song, Grivainis, Mark, Ding, Li, LaCava, John, Burns, Kathleen H., Boeke, Jef D., Fenyo, David |
| المصدر: | McKerrow , W , Wang , X , Mendez-Dorantes , C , Mita , P , Cao , S , Grivainis , M , Ding , L , LaCava , J , Burns , K H , Boeke , J D & Fenyo , D 2022 , ' LINE-1 expression in cancer correlates with p53 mutation, copy number alteration, and S phase checkpoint ' , Proceedings of the National Academy of Sciences of the United States of America , vol. 119 , no. 8 , e2115999119 . https://doi.org/10.1073/pnas.2115999119Test |
| سنة النشر: | 2022 |
| المجموعة: | University of Groningen research database |
| مصطلحات موضوعية: | retrotransposon, LINE-1, cancer, DNA damage response, copy number alteration, INTEGRATED PROTEOGENOMIC CHARACTERIZATION, L1 RETROTRANSPOSITION, DNA-REPAIR, REVERSE TRANSCRIPTION, ATM, PHOSPHORYLATION, GENE, SMC1, AUTOPHOSPHORYLATION, PROTEINS |
| الوصف: | Retrotransposons are genomic DNA sequences that copy them-selves to new genomic locations via RNA intermediates; LINE-1 is the only active and autonomous retrotransposon in the human genome. The mobility of LINE-1 is largely repressed in somatic tissues but is derepressed in many cancers, where LINE-1 retrotransposition is correlated with p53 mutation and copy number alteration (CNA). In cell lines, inducing LINE-1 expression can cause double-strand breaks (DSBs) and replication stress. Reanalyzing multiomic data from breast, ovarian, endometrial, and colon cancers, we confirmed correlations between LINE-1 expression, p53 mutation status, and CNA. We observed a consistent correlation between LINE-1 expression and the abundance of DNA replication complex components, indicating that LINE-1 may also induce replication stress in human tumors. In endometrial cancer, high-quality phosphoproteomic data allowed us to identify the DSB-induced ATM-MRN-SMC S phase checkpoint pathway as the primary DNA damage response (DDR) pathway associated with LINE-1 expres-sion. Induction of LINE-1 expression in an in vitro model led to increased phosphorylation of MRN complex member RAD50, suggesting that LINE-1 directly activates this pathway. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://research.rug.nl/en/publications/53227d52-bf4e-4ff9-9d05-eafbec03b01cTest |
| DOI: | 10.1073/pnas.2115999119 |
| الإتاحة: | https://doi.org/10.1073/pnas.2115999119Test https://hdl.handle.net/11370/53227d52-bf4e-4ff9-9d05-eafbec03b01cTest https://research.rug.nl/en/publications/53227d52-bf4e-4ff9-9d05-eafbec03b01cTest https://pure.rug.nl/ws/files/217831018/pnas.2115999119.pdfTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.23705402 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1073/pnas.2115999119 |
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