Artículo
TDP1 suppresses chromosomal translocations and cell death induced by abortive TOP1 activity during gene transcription
Autor/es | Rubio Contreras, Diana
Gómez Herreros, Fernando |
Departamento | Universidad de Sevilla. Departamento de Genética |
Fecha de publicación | 2023-11-09 |
Fecha de depósito | 2024-05-21 |
Publicado en |
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Resumen | DNA topoisomerase I (TOP1) removes torsional stress by transiently cutting one DNA strand. Such cuts are rejoined by TOP1 but can occasionally become abortive generating permanent protein-linked single strand breaks (SSBs). ... DNA topoisomerase I (TOP1) removes torsional stress by transiently cutting one DNA strand. Such cuts are rejoined by TOP1 but can occasionally become abortive generating permanent protein-linked single strand breaks (SSBs). The repair of these breaks is initiated by tyrosyl-DNA phosphodiesterase 1 (TDP1), a conserved enzyme that unlinks the TOP1 peptide from the DNA break. Additionally, some of these SSBs can result in double strand breaks (DSBs) either during replication or by a poorly understood transcription-associated process. In this study, we identify these DSBs as a source of genome rearrangements, which are suppressed by TDP1. Intriguingly, we also provide a mechanistic explanation for the formation of chromosomal translocations unveiling an error-prone pathway that relies on the MRN complex and canonical non-homologous end-joining. Collectively, these data highlight the threat posed by TOP1-induced DSBs during transcription and demonstrate the importance of TDP1-dependent end-joining in protecting both gene transcription and genome stability. |
Agencias financiadoras | Ministerio de Ciencia e Innovación (MICIN). España Agencia Estatal de Investigación. España Junta de Andalucía |
Identificador del proyecto | PID2019-105212GB-I00
P20_00561 |
Cita | Rubio Contreras, D. y Gómez Herreros, F. (2023). TDP1 suppresses chromosomal translocations and cell death induced by abortive TOP1 activity during gene transcription. Nature Communications, 14 (1), 6940. https://doi.org/10.1038/s41467-023-42622-7. |
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