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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.

SUBMITTER: Patil M

PROVIDER: S-EPMC3865050 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Nek1 interacts with Ku80 to assist chromatin loading of replication factors and S-phase progression.

Patil Mallikarjun M Pabla Navjotsingh N Ding Han-Fei HF Dong Zheng Z

Cell cycle (Georgetown, Tex.) 20130710 16

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 ...[more]

PMID: 23851348

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