title: Myosin 16 levels fluctuate during the cell cycle and are downregulated in response to DNA replication stress.
abstract: Myosins comprise a highly conserved superfamily of eukaryotic actin-dependent motor proteins implicated in a large repertoire of functions in both the cytoplasm and the nucleus. Class XVI myosin, MYO16, reveals expression in most somatic as well as meiotic cells with prominent localization in the nucleus, excepting the nucleolus; however, the role(s) of Myo16 in the nucleus remain unknown. In this report, we investigated Myo16 abundance during transit through the cell cycle. Immunolocalization, immunoblot, flow cytometric and quantitative RT-PCR studies performed in Rat2 cells indicate that Myo16 mRNA and protein abundance are cell cycle regulated: in the unperturbed cell cycle, each rises to peak levels in late G1 and thereon through S-phase and each decays as cells enter M-phase. Notably, RNA interference-induced Myo16 depletion results in altered cell cycle distribution as well as in large-scale cell death. In response to DNA replication stress (impaired replication fork progression as a consequence of DNA damage, lack of sufficient deoxynucleotides, or inhibition of DNA polymerases), Myo16 protein shows substantial loss. Attenuation of replication stress (aphidicolin or hydroxyurea) is followed by a recovery of Myo16 expression and resumption of S-phase progression. Collectively, these observations suggest that Myo16 may play a regulatory role in cell cycle progression.
authors.affiliation: Institute of Molecular Medicine and Genetics, Department of Medicine, Georgia Regents University, Medical College of Georgia, Augusta, Georgia 30912, USA. rcameron@gru.edu
authors.forename: Richard S
authors.initials: RS
authors.lastname: Cameron
authors.forename: Changdan
authors.initials: C
authors.lastname: Liu
authors.forename: Jeanene P S
authors.initials: JP
authors.lastname: Pihkala
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004249:DNA Damage; D004261:DNA Replication; D015536:Down-Regulation; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D055550:Protein Stability; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013312:Stress, Physiological / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; C483469:MYH16 protein, human; D012333:RNA, Messenger; D018995:Myosin Heavy Chains
keywords: DNA damage response; cell cycle; myosin XVI; nucleus