Widespread alteration of the genomic DNA is a hallmark of tumors, and alteration of genes involved in DNA maintenance have been shown to contribute to the tumorigenic process. The DNA polymerase of Saccharomyces cerevisiae is required for error-prone repair following DNA damage and consists of a complex between three proteins, scRev1, scRev3, and scRev7. Here we describe a candidate human homolog of S. cerevisiae Rev7 (hREV7), which was identified in a yeast two-hybrid screen using the human homolog of S. cerevisiae Rev3 (hREV3). The hREV7 gene product displays 23% identity and 53% similarity with scREV7, as well as 23% identity and 54% similarity with the human mitotic checkpoint protein hMAD2. hREV7 is located on human chromosome 1p36 in a region of high loss of heterozygosity in human tumors, although no alterations of hREV3 or hREV7 were found in primary human tumors or human tumor cell lines. The interaction domain between hREV3 and hREV7 was determined and suggests that hREV7 probably functions with hREV3 in the human DNA polymerase complex. In addition, we have identified an interaction between hREV7 and hMAD2 but not hMAD1. While overexpression of hREV7 does not lead to cell cycle arrest, we entertain the possibility that it may act as an adapter between DNA repair and the spindle assembly checkpoint. DNA damage is induced by a variety of endogenous and exogenous factors (1). Such DNA alterations include reactive oxygen damage, deamination, loss of nucleotides, nucleotide modifications, and DNA strand breaks. DNA damage repair has evolved to cope with these environmental and mutageninduced DNA alteration and plays a central role in maintaining the genetic stability of the organism (2, 3).Extensive studies of bacterial and yeast systems have identified components of the DNA repair machinery. In the yeast Saccharomyces cerevisiae, pyrimidine dimers induced by UV radiation damage are corrected by the RAD3 excision repair, the RAD6 postreplication repair, and the RAD52 recombinational repair pathways (for a review see Ref. 4). Interestingly, the removal of UV damage by the RAD6 pathway occurs by both error-free and error-prone (mutagenic) mechanisms (5, 6). The mutagenic repair of UV damage has been shown to require the UV revertible genes, REV1, REV3, and REV7, a lesion bypass polymerase complex consisting of a deoxycytidyl-transferase (Rev1), a polymerase catalytic subunit (Rev3), and a polymerase accessory protein (Rev7) (for review see Refs. 7 and 8). This polymerase complex has been termed polymerase .