During the first month of the closures, starting Tuesday, April 22, you probably can safely take your regular route to work, because only eastbound freeway lanes will be closed then.
The real question during those first weeks is: What is your best route home? If you typically use the freeway to get home, you could try winding through city streets to an on-ramp east of the closure site (the freeway closures are from about 18th to 24th streets). Or how about plotting a route through surface streets to get you to the Stockton Boulevard onramp eastbound?
There is the X Street onramp at 27th Street to eastbound Highway 50. But X Street may be jammed. You might try heading east on surface streets to get to Folsom or J or H streets and head east on those. Any way you choose, just expect to go slow.