Roles of POLD4, smallest subunit of DNA polymerase delta, in nuclear structures and genomic stability of human cells.
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.
Huang
Qin Miao
QM
Division of Molecular Carcinogenesis, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Akashi
Tomohiro
T
Masuda
Yuji
Y
Kamiya
Kenji
K
Takahashi
Takashi
T
Suzuki
Motoshi
M
D002453:Cell Cycle / Q000235:genetics*; D002467:Cell Nucleus / Q000201:enzymology / Q000235:genetics* / Q000648:ultrastructure; D049109:Cell Proliferation; D004258:DNA Polymerase III / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication / Q000235:genetics*; D042822:Genomic Instability / Q000235:genetics*; D006801:Humans; D034741:RNA, Small Interfering / Q000235:genetics
D034741:RNA, Small Interfering; C521101:POLD4 protein, human; D004258:DNA Polymerase III