Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair

Ubiquitin-conjugating enzyme variant (UEV) proteins resemble ubiquitin-conj ugating enzymes (E2s) but lack the defining E2 active-site residue. The MMS 2-encoded UEV protein has been genetically implicated in error-free postrep licative DNA repair in Saccharomyces cerevisiae. We show that Mms2p forms a specific heteromeric complex with the UBC13-encoded E2 and is required for the Ubc13p-dependent assembly of polyubiquitin chains linked through lysin e 63. A ubc13 yeast strain is UV sensitive, and single, double, and triple mutants of the UBC13, MMS2, and ubiquitin (ubiK63R) genes display a compara ble phenotype. These findings support a model in which an Mms2p/Ubc13p comp lex assembles novel polyubiquitin chains for signaling in DNA repair, and t hey suggest that UEV proteins may act to increase diversity and selectivity in ubiquitin conjugation.