Topoisomerase 1 activity during mitotic transcription favors the transition from mitosis to G1.
Mol Cell
; 81(24): 5007-5024.e9, 2021 12 16.
Article
em En
| MEDLINE
| ID: mdl-34767771
ABSTRACT
As cells enter mitosis, chromatin compacts to facilitate chromosome segregation yet remains transcribed. Transcription supercoils DNA to levels that can impede further progression of RNA polymerase II (RNAPII) unless it is removed by DNA topoisomerase 1 (TOP1). Using ChIP-seq on mitotic cells, we found that TOP1 is required for RNAPII translocation along genes. The stimulation of TOP1 activity by RNAPII during elongation allowed RNAPII clearance from genes in prometaphase and enabled chromosomal segregation. Disruption of the TOP1-RNAPII interaction impaired RNAPII spiking at promoters and triggered defects in the post-mitotic transcription program. This program includes factors necessary for cell growth, and cells with impaired TOP1-RNAPII interaction are more sensitive to inhibitors of mTOR signaling. We conclude that TOP1 is necessary for assisting transcription during mitosis with consequences for growth and gene expression long after mitosis is completed. In this sense, TOP1 ensures that cellular memory is preserved in subsequent generations.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
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RNA Polimerase II
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Neoplasias Colorretais
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Fase G1
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DNA Topoisomerases Tipo I
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Montagem e Desmontagem da Cromatina
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Proliferação de Células
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Mitose
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Mol Cell
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Suécia