Roles of POLD4, smallest subunit of DNA polymerase delta, in nuclear structures and genomic stability of human cells.

Biochemical and Biophysical Research Communications
Qin Miao HuangMotoshi Suzuki

Abstract

Mammalian DNA polymerase delta (pol delta) is essential for DNA replication, though the functions of this smallest subunit of POLD4 have been elusive. We investigated pol delta activities in vitro and found that it was less active in the absence of POLD4, irrespective of the presence of the accessory protein PCNA. shRNA-mediated reduction of POLD4 resulted in a marked decrease in colony formation activity by Calu6, ACC-LC-319, and PC-10 cells. We also found that POLD4 reduction was associated with an increased population of karyomere-like cells, which may be an indication of DNA replication stress and/or DNA damage. The karyomere-like cells retained an ability to progress through the cell cycle, suggesting that POLD4 reduction induces modest genomic instability, while allowing cells to grow until DNA damage reaches an intolerant level. Our results indicate that POLD4 is required for the in vitro pol delta activity, and that it functions in cell proliferation and maintenance of genomic stability of human cells.

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Citations

Dec 10, 2015·The Journal of Clinical Investigation·Motoshi SuzukiTakashi Takahashi
Apr 22, 2015·Environment International·Somnath Paul, Ashok K Giri
Jul 25, 2017·Genes·Marietta Y W T LeeErnest Y C Lee
Sep 10, 2020·Journal of Cellular and Molecular Medicine·Motoshi SuzukiTakashi Takahashi
Sep 12, 2013·The Journal of Biological Chemistry·Kenta TeraiAnindya Dutta
Jul 18, 2012·Cell Cycle·Jennifer CheaMarietta Y W T Lee
Oct 11, 2012·Environmental and Molecular Mutagenesis·Marietta Y W T LeeErnest Y C Lee
Sep 24, 2010·Cancer Research·Qin Miao HuangMotoshi Suzuki
Jul 22, 2019·DNA Repair·Marietta Y W T LeeErnest Y C Lee
Apr 23, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Yuki TakagawaJohji Inazawa
Sep 13, 2012·Mutation Research·Motoshi Suzuki, Takashi Takahashi

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