It happened around 6 a.m. in the eastbound lanes between Exits 15 and 17 in Franklin Square.
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Police say the vehicle left the parkway, careened through a wooded area and ended up back on the roadway.
It then struck a tree, ejecting the driver.
Video from NewsCopter 7 showed the vehicle on its side. Multiple police and rescue units were on the scene.
The driver, identified as 28-year-old Ashlee Tessono, of North Baldwin, was rushed to Nassau University Medical Center, where she succumbed to her injuries.
Two eastbound lanes remained open during the New York State Police investigation.
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The crash caused an extensive backup in the eastbound lanes and lesser delays on the westbound side.
Accident investigators were working to determine what caused the driver to lose control.
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