Synthesis and Characterization of Specific Reverse Transcriptase Inhibitors for Mammalian LINE-1 Retrotransposons
| Autor: | Valentin Sanchez-Carnerero, Carmen Salvador-Palomeque, Juan A. Tamayo, Pablo Tristan-Ramos, Laura Sánchez, Guillermo Banuelos-Sanchez, Jose L. Garcia-Perez, Maria Benitez-Guijarro, Santiago Morell, Jose L. Garcia-Puche, Francisco Franco-Montalban, Sara R. Heras, Meriem Benkaddour-Boumzaouad |
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| Rok vydání: | 2019 |
| Předmět: |
Transposable element
Clinical Biochemistry Retrotransposon Biology brain genomic mosaicism 01 natural sciences Biochemistry Genome Germline Cell Line LINE-1 retrotransposition reverse transcriptase Drug Discovery cancer Humans Molecular Biology Pharmacology Genetics Molecular Structure 010405 organic chemistry nucleoside analog food and beverages RNA LTR-retrotransposon Dideoxynucleosides Reverse transcriptase Long terminal repeat 0104 chemical sciences Long interspersed nuclear element HEK293 Cells Long Interspersed Nucleotide Elements Reverse Transcriptase Inhibitors Molecular Medicine HeLa Cells |
| Zdroj: | Cell Chemical Biology. 26:1095-1109.e14 |
| ISSN: | 2451-9456 |
| DOI: | 10.1016/j.chembiol.2019.04.010 |
| Popis: | Retrotransposons are a type of transposable element (TE) that have amplified to astonishing numbers in mammalian genomes, comprising more than a third of the human and mouse genomes. Long interspersed element class 1 (LINE-1 or L1) retrotransposons are abundant and currently active retroelements in the human and mouse genomes. Similarly, long terminal repeat (LTR)-containing retrotransposons are abundant in both genomes, although only active in mice. LTR- and LINE-1-retroelements use different mechanisms for retrotransposition, although both involve the reverse transcription of an intermediate retroelement-derived RNA. Retrotransposon activity continues to effect the germline and somatic genomes, generating interindividual variability over evolution and potentially influencing cancer and brain physiology, respectively. However, relatively little is known about the functional consequences of retrotransposition. In this study, we have synthesized and characterized reverse transcriptase inhibitors specific for mammalian LINE-1 retrotransposons, which might help deciphering the functional impact of retrotransposition in vivo. |
| Databáze: | OpenAIRE |
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