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Cell Chem Biol ; 26(8): 1095-1109.e14, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31155508

RESUMO

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.


Assuntos
Didesoxinucleosídeos/farmacologia , Elementos Nucleotídeos Longos e Dispersos/efeitos dos fármacos , Inibidores da Transcriptase Reversa/farmacologia , Linhagem Celular , Didesoxinucleosídeos/síntese química , Didesoxinucleosídeos/química , Células HEK293 , Células HeLa , Humanos , Estrutura Molecular , Inibidores da Transcriptase Reversa/síntese química , Inibidores da Transcriptase Reversa/química
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