HHR23A, THE HUMAN HOMOLOG OF THE YEAST REPAIR PROTEIN RAD23, INTERACTS SPECIFICALLY WITH VPR PROTEIN AND PREVENTS CELL-CYCLE ARREST BUT NOTTHE TRANSCRIPTIONAL EFFECTS OF VPR

Yeast two-hybrid selection of proteins interacting with human immunode ficiency virus type 1 Vpr identified HHR23A, a human homologue of the yeast DNA repair protein RAD23, as a specific interactor. A small 57-a mino-acid C-terminal portion of HHR23A was sufficient for Vpr interact ion. When introduced into human cells by transfection, full-length HHR 23A or its C-terminal fragments were able to alleviate Vpr-induced cel l cycle arrest, suggesting that HHR23A may participate in the pathway leading to G2 arrest by Vpr. We have also examined the effects of HHR2 3 on the recently identified transcription coactivator function of Vpr . The two Vpr functions are independent, since we have identified muta nts lacking either the cell cycle arrest or the coactivator function. Our analysis showed that excess of HHR23A does not affect the coactiva tor function of Vpr, while it affects the cell cycle arresting functio n. Therefore, a simple sequestering model for Vpr in the presence of e xcess HHR23A is not supported, we propose that the interaction of HHR2 3A with Vpr may affect specifically pathways leading to cell cycle reg ulation. (C) 1998 Academic Press.