There was a issue in some versions of ePO 4.6 that in some cases Apache would fail to properly query the domain controller when processing Policy Assignment Rules. This was fixed in ePO 5.1.0. Likely in this case the query to the DC is taking longer than expected and timed out.
Database mirroring captures the data in the DC and stores it in the ePO database and rather than querying the DC to process the Policy Assignment Rule it queries the ePO Database. The upside of this is a significant performance increase but the downside is the replication of the Domain Controller will only occur when the LdapSync: Sync Across Users server task is run. In most cases this isn't a problem.