TY - JOUR
T1 - Roles of POLD4, smallest subunit of DNA polymerase δ, in nuclear structures and genomic stability of human cells
AU - Huang, Qin Miao
AU - Akashi, Tomohiro
AU - Masuda, Yuji
AU - Kamiya, Kenji
AU - Takahashi, Takashi
AU - Suzuki, Motoshi
N1 - Funding Information:
We thank Keiko Ueda and Makiko Terada for their initial involvement in this project. We are also grateful for Dr. Takeshi Senga of our university for the critical reading of the manuscript. This work was supported in part by a Grant-in-Aid for Scientific Research on Innovative Areas, a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science, and Technology of Japan , and a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science .
PY - 2010/1/1
Y1 - 2010/1/1
N2 - Mammalian DNA polymerase δ (pol δ) is essential for DNA replication, though the functions of this smallest subunit of POLD4 have been elusive. We investigated pol δ 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 δ activity, and that it functions in cell proliferation and maintenance of genomic stability of human cells.
AB - Mammalian DNA polymerase δ (pol δ) is essential for DNA replication, though the functions of this smallest subunit of POLD4 have been elusive. We investigated pol δ 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 δ activity, and that it functions in cell proliferation and maintenance of genomic stability of human cells.
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U2 - 10.1016/j.bbrc.2009.11.094
DO - 10.1016/j.bbrc.2009.11.094
M3 - Article
C2 - 19931513
AN - SCOPUS:72949101986
SN - 0006-291X
VL - 391
SP - 542
EP - 546
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -