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The Blackwall Tunnel is set to be partially closed over three weekends.
Works for the new Silvertown Tunnel will see the tunnel closed southbound.
The closures have been announced by Transport for London (TFL) with the first taking place this weekend – Saturday, February 24 through to Sunday, February 25.
There will also be closures from Saturday, March 16 to Sunday, March 18 and Saturday, April 13 to Sunday, April 15.
On each occasion, the tunnel will be closed from 12.01am on Saturday and reopened by 5am on the Monday.
The works are required to implement the road configuration for the new Silvertown Tunnel, which will open in 2025.
New over-height vehicle gantries will be installed that will protect the tunnel while resurfacing works are part of the final road configuration.
The new tunnel will provide a public transport-focused river crossing with zero-emission bus links across the Thames.
Once open the crossing, which is within the Ultra-Low Emission Zone (UlEZ) and will be subject to a user charge, will also reduce congestion and improve the reliability and resilience of the Blackwall Tunnel.
This will improve overall air quality in the local area, TfL says.
Drivers are advised to plan their routes in advance, checking before they travel so they can consider any other potential traffic impacts or restrictions.
Meanwhile, drivers of HGVs and vans more than two metres in height or weighing more than two tonnes are advised to consider routes away from central London across the weekends where possible.
Carl Eddleston, from TfL, said: “We appreciate that these planned weekend works will have an impact on some drivers and are doing everything in our power to limit potential disruption and complete these essential works as quickly as possible, including ensuring a northbound route through the Blackwall Tunnel is maintained throughout.”