کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1179476 | 962779 | 2006 | 7 صفحه PDF | دانلود رایگان |
DNA polymerase α (pol-α) is a heterotetrameric enzyme (p180–p68–p58–p48 in mouse) that is essential for the initiation of chain elongation during DNA replication. The catalytic (p180) and p68 subunits of pol-α are phosphorylated by Cdk–cyclin complexes, with p68 being hyperphosphorylated by cyclin-dependent kinases in G2 phase of the cell cycle. The activity of Cdk2–cyclin A increases during late S phase and peaks in G2 phase. We have now examined the role of p68 in the interaction between the catalytic subunit of pol-α and hyperphosphorylated retinoblastoma protein (ppRb) and in the stimulation of the polymerase activity of pol-α by ppRb. With the use of recombinant proteins, we found that nonphosphorylated p68 inhibited the stimulation of pol-α activity by ppRb, suggesting that p68 might impede the association of ppRb with p180. Phosphorylation of p68 by Cdk2–cyclin A greatly reduced its inhibitory effect. Immunofluorescence analysis also revealed that ppRb localized at sites of DNA replication specifically in late S phase. These results suggest that Cdk–cyclin A can phosphorylate pol-α which may result in a conformational change in pol-α facilitating its interaction with and activation by ppRb.
Journal: Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics - Volume 1764, Issue 9, September 2006, Pages 1447–1453