期刊
NATURE STRUCTURAL & MOLECULAR BIOLOGY
卷 26, 期 1, 页码 58-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41594-018-0170-1
关键词
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资金
- Agence Nationale de la Recherche [ANR-13-BSV6-0008-01/FRA-Dom, ANR-15-CE12-0004-01]
- Association pour la Recherche sur le Cancer [Sl220130607073, PGA120150202272]
- Institut National du Cancer [2013-103, PLBIO17-194]
- Ministere de l'Enseignement Superieur et de la Recherche
- Ligue contre le cancer
- Agence Nationale de la Recherche (ANR) [ANR-15-CE12-0004] Funding Source: Agence Nationale de la Recherche (ANR)
Common fragile sites (CFSs) are loci that are hypersensitive to replication stress and hotspots for chromosomal rearrangements in cancers. CFSs replicate late in S phase, are cell-type specific and nest in large genes. The relative impact of transcription-replication conflicts versus a low density in initiation events on fragility is currently debated. Here we addressed the relationships between transcription, replication, and instability by manipulating the transcription of endogenous large genes in chicken and human cells. We found that inducing low transcription with a weak promoter destabilized large genes, whereas stimulating their transcription with strong promoters alleviated instability. Notably, strong promoters triggered a switch to an earlier replication timing, supporting a model in which high transcription levels give cells more time to complete replication before mitosis. Transcription could therefore contribute to maintaining genome integrity, challenging the dominant view that it is exclusively a threat.
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