Starting Monday Nov. 14, Clarke Road will be closed between Oxford Street East and Cheapside Street.
The City of London says the closure is to allow CN Rail to make repairs to the railway crossing.
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The road is set to reopen by the evening of Friday Nov. 18.
During this time, drivers will be detoured around the closure using Oxford Street East, Veterans Memorial Parkway and Huron Street.
The sidewalks will also be closed.
Local businesses will remain open.