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- Title
Distinctive activities of DNA polymerases during human DNA replication.
- Authors
Rytkönen, Anna K.; Vaara, Markku; Nethanel, Tamar; Kaufmann, Gabriel; Sormunen, Raija; Läär, Esa; Nasheuer, Heinz-Peter; Rahmeh, Amal; Lee, Marietta Y. W. T.; Syväoja, Juhani E.; Pospiech, Helmut
- Abstract
The contributions of human DNA polymerases (pols) α, δ and ε during S-phase progression were studied in order to elaborate how these enzymes co-ordinate their functions during nuclear DNA replication. Pol δ was three to four times more intensely UV cross-linked to nascent DNA in late compared with early S phase, whereas the cross-linking of pols α and ε remained nearly constant throughout the S phase. Consistently, the chromatin-bound fraction of pol δ, unlike pols α and ε, increased in the late S phase. Moreover, pol δ neutralizing antibodies inhibited replicative DNA synthesis most efficiently in late S-phase nuclei, whereas antibodies against pol ε were most potent in early S phase. Ultrastructural localization of the pols by immuno-electron microscopy revealed pol ε to localize predominantly to ring-shaped clusters at electron-dense regions of the nucleus, whereas pol δ was mainly dispersed on fibrous structures. Pol α and proliferating cell nuclear antigen displayed partial colocalization with pol δ and ε, despite the very limited colocalization of the latter two pols. These data are consistent with models where pols δ and ε pursue their functions at least partly independently during DNA replication.
- Subjects
DNA polymerases; DNA replication; CELL cycle; ELECTRON microscopy; ENZYMES
- Publication
FEBS Journal, 2006, Vol 273, Issue 13, p2984
- ISSN
1742-464X
- Publication type
Article
- DOI
10.1111/j.1742-4658.2006.05310.x