title: The MCM-associated protein MCM-BP is important for human nuclear morphology.
abstract: Mini-chromosome maintenance complex-binding protein (MCM-BP) was discovered as a protein that is strongly associated with human MCM proteins, known to be crucial for DNA replication in providing DNA helicase activity. The Xenopus MCM-BP homologue appears to play a role in unloading MCM complexes from chromatin after DNA synthesis; however, the importance of MCM-BP and its functional contribution to human cells has been unclear. Here we show that depletion of MCM-BP by sustained expression of short hairpin RNA (shRNA) results in highly abnormal nuclear morphology and centrosome amplification. The abnormal nuclear morphology was not seen with depletion of other MCM proteins and was rescued with shRNA-resistant MCM-BP. MCM-BP depletion was also found to result in transient activation of the G2 checkpoint, slowed progression through G2 and increased replication protein A foci, indicative of replication stress. In addition, MCM-BP depletion led to increased cellular levels of MCM proteins throughout the cell cycle including soluble MCM pools. The results suggest that MCM-BP makes multiple contributions to human cells that are not limited to unloading of the MCM complex.
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Canada.
authors.forename: Madhav
authors.initials: M
authors.lastname: Jagannathan
authors.forename: Amos M
authors.initials: AM
authors.lastname: Sakwe
authors.forename: Tin
authors.initials: T
authors.lastname: Nguyen
authors.forename: Lori
authors.initials: L
authors.lastname: Frappier
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D002467:Cell Nucleus / Q000378:metabolism; D053144:Cell Nucleus Shape; D018385:Centrosome / Q000378:metabolism; D004261:DNA Replication; D059565:G2 Phase Cell Cycle Checkpoints; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051716:Replication Protein A / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C519407:MCMBP protein, human; D009687:Nuclear Proteins; D051716:Replication Protein A