title: Nek1 interacts with Ku80 to assist chromatin loading of replication factors and S-phase progression.
abstract: NIMA-related kinases (Neks) play divergent roles in mammalian cells. While several Neks regulate mitosis, Nek1 was reported to regulate DNA damage response, centrosome duplication and primary cilium formation. Whether Nek1 participates in cell cycle regulation is not known. Here we report that loss of Nek1 results in severe proliferation defect due to a delay in S-phase of the cell cycle. Nek1-deficient cells show replication stress and checkpoint activation under normal growth conditions. Nek1 accumulates on the chromatin during normal DNA replication. In response to replication stress, Nek1 is further activated for chromatin localization. Nek1 interacts with Ku80 and, in Nek1-deficient cells chromatin localization of Ku80 and several other DNA replication factors is significantly reduced. Thus, Nek1 may facilitate S-phase progression by interacting with Ku80 and regulating chromatin loading of replication factors.
authors.affiliation: Department of Cellular Biology and Anatomy, Medical College of Georgia, Georgia Regents University and Charlie Norwood Veterans Affairs Medical Center, Augusta, GA, USA.
authors.forename: Mallikarjun
authors.initials: M
authors.lastname: Patil
authors.forename: Navjotsingh
authors.initials: N
authors.lastname: Pabla
authors.forename: Han-Fei
authors.initials: HF
authors.lastname: Ding
authors.forename: Zheng
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D000071877:Checkpoint Kinase 1; D002843:Chromatin / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004847:Epithelial Cells; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D000072200:Ku Autoantigen; D051379:Mice; D000072380:NIMA-Related Kinase 1; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D059807:S Phase Cell Cycle Checkpoints / Q000502:physiology*
chemical_list: D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; C475961:gamma-H2AX protein, mouse; D011494:Protein Kinases; D000071877:Checkpoint Kinase 1; C000606914:NEK1 protein, human; D000072380:NIMA-Related Kinase 1; C000606920:Nek1 protein, mouse; D017346:Protein Serine-Threonine Kinases; C000606509:Xrcc6 protein, human; C000606510:Xrcc6 protein, mouse; D000072200:Ku Autoantigen
keywords: DNA replication; Ku80; Nek1; S-phase; cell cycle