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The wreck was first reported just before 6:45 a.m. Friday.
Officers said Cassandra Moseley, the driver of a Chevy TrailBlazer was seriously injured and her passenger, 70-year-old Frances Moseley, was killed.
Durham Police said the driver of a Ford F-150, 67-year-old Vernon Smith Jr., lost control while going east onto US 15-501 South and struck the Trailblazer.
Smith, of Graham, was charged with misdemeanor death and careless and reckless driving, Smith had no signs of impairment, Durham Police said.
Cassandra Moseley, of Norlina, was taken to Duke Hospital with serious injuries but was described as stable.
A black Mercedes driven by Angela Carlton-Campbell, crashed after it was struck by a wheelchair that flew out of Smith's pickup after impact.
Smith and Campbell were taken to Duke Hospital with serious but not life-threatening injuries.
The fatal crash closed all lanes US 15-501 near US 70 for several hours as debris stretched across all lanes.
"I saw the pickup truck and car went in front of me ... the truck was pushing the car," said Juan Hortas, who was nearly involved in the crash. He said the TrailBlazer flipped.
The roadway reopened about 11 a.m.
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Those with any information are asked to call investigator Kozar at (919) 560-4935, ext. 29450 or CrimeStoppers at (919) 683-1200.