 DDB2 is a DCAF protein and is both a ubiquitination substrate of the CRL4 complex and also serves as an E3 ligase protein for other substrates such as XPC and histones (see next section) near the damage site.Due to its ubiquitination of DNA damage-recognizing proteins DDB2 and XPC, CUL4A has been described as a negative regulator of NER activity.In addition to the "global" type of NER, the CRL4A complex also appears to play a role in "transcription-coupled" NER in conjunction with the Cockayne Syndrome A protein.