A human REV7 homolog that interacts with the polymerase zeta catalytic subunit hREV3 and the spindle assembly checkpoint protein hMAD2

Widespread alteration of the genomic DNA is a hallmark of tumors, and alter ation of genes involved in DNA maintenance have been shown to contribute to the tumorigenic process. The DNA polymerase xi 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 describ e a candidate human homolog of S. cerevisiae Rev7 (hREV7), which was identi fied in a yeast two-hybrid screen using the human homolog of S. cerevisiae Rev3 (hREV3), The hREV7 gene product displays 23% identity and 53% similari ty with scREV7, as well as 23% identity and 54% similarity with the human m itotic checkpoint protein hMAD2. hREV7 is located on human chromosome 1p36 in a region of high loss of heterozygosity in human tumors, although no alt erations of hREV3 or hREV7 were found in primary human tumors or human tumo r cell lines. The interaction domain between hREV3 and hREV7 was determined and suggests that hREV7 probably functions with hREV3 in the human DNA pol ymerase xi 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 ad apter between DNA repair and the spindle assembly checkpoint.