Knockdown of RMI1 impairs DNA repair under DNA replication stress
Autor: | Lianying Fang, Mengmeng Yang, Changyan Xiao, Chang Xu, Qiang Liu, Yangyang Kong, Liqing Du |
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Rok vydání: | 2017 |
Předmět: |
DNA Replication
0301 basic medicine Genome instability DNA Repair Cell Survival DNA repair Biophysics Eukaryotic DNA replication Biology Biochemistry Genomic Instability 03 medical and health sciences 0302 clinical medicine Replication factor C Control of chromosome duplication Stress Physiological Humans Hydroxyurea Molecular Biology Replication protein A DNA replication Nuclear Proteins Cell Cycle Checkpoints Cell Biology Molecular biology DNA-Binding Proteins 030104 developmental biology Gene Knockdown Techniques 030220 oncology & carcinogenesis Origin recognition complex Rad51 Recombinase Carrier Proteins DNA Damage HeLa Cells |
Zdroj: | Biochemical and Biophysical Research Communications. 494:158-164 |
ISSN: | 0006-291X |
DOI: | 10.1016/j.bbrc.2017.10.062 |
Popis: | RMI1 (RecQ-mediated genome instability protein 1) forms a conserved BTR complex with BLM, Topo IIIα, and RMI2, and its absence causes genome instability. It has been revealed that RMI1 localizes to nuclear foci with BLM and Topo IIIα in response to replication stress, and that RMI1 functions downstream of BLM in promoting replication elongation. However, the precise functions of RMI1 during replication stress are not completely understood. Here we report that RMI1 knockdown cells are hypersensitive to hydroxyurea (HU). Using comet assay, we show that RMI1 knockdown cells exhibit accumulation of broken DNAs after being released from HU treatment. Moreover, we demonstrate that RMI1 facilitates the recovery from activated checkpoint and resuming the cell cycle after replicative stress. Surprisingly, loss of RMI1 results in a failure of RAD51 loading onto DNA damage sites. These findings reveal the importance of RMI1 in response to replication stress, which could explain the molecular basis for its function in maintaining genome integrity. |
Databáze: | OpenAIRE |
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