Assignment of REV3 to DNA damage response pathways. REV3 and RAD5 are known to participate in alternative pathways in reaction to MMC- (A), MMS- (B), and cisplatin-induced (C) damage. A, We found that, in response to MMC-induced interstrand cross links, REV3 functions in pathways containing either RECQ4A or MUS81, respectively. B, MMS-induced alkylated bases are repaired or bypassed by at least three alternate pathways. We were able to assign REV3 to the pathway containing MUS81, whereas RECQ4A is not epistatic to REV3. C, Cisplatin mainly causes intrastrand cross links. Recent work suggested at least three separate pathways in response to such cross links with the proteins RECQ4A, MUS81, and RAD5A as key factors. Here, we revealed a fourth pathway that is characterized by the participation of REV3.