Interaction Of The Regulatory Subunit Of Ribonucleotide Reductase With Minichromosome Maintenance Complexes Regulate Cell Growth
Abstract
We discovered a novel interaction between ribonucleotide reductase subunit 1 (R1) and the catalytic minichromosome maintenance proteins (MCM4/6/7) by in vitro binding and co-immunoprecipiation in various mammalian cell lines. We observed that R1 colocalizes with MCM4/6/7 in mitotic cells, and in non-mitotic cells, R1 only co-localizes with MCM7 in the cytosol. When R1 expression is inducibly knocked down in the presence of dNTPs, we see a decline in MCM7 expression and reduced cell proliferation. We surmise that there are two R1-MCM complexes: a cytoplasmic R1-MCM7 complex and an M-phase associated R1-MCM4/6/7 complex. Our work has demonstrated that R1 stabilizes MCM7 which underscores a secondary R1 function that is independent of its role in ribonucleotide reductase.