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There are a few reasons why this may be happening.
Many times if you're experiencing a large amount of traffic, this can take down your database server, and hence, your entire site. Sites like http://digg.com and http://slashdot.com are particularly notorious for this. If this is the case, congratulations, you're popular!
If you've ruled out all of the above, you have two options left.
You can contact your host and ask them for help, or you could even find help at the Expanse Forums.