Characterizing the mechanism of continued primer synthesis at stalled replication forks and its contribution to checkpoint activation
Abstract/Contents
- Abstract
- Stalled replication forks activate and are stabilized by the ATR-mediated checkpoint, but ultimately they must also recover from the arrest. While primed ssDNA is sufficient for checkpoint activation, it is still unknown how this signal is generated at a stalled replication fork. Furthermore, it is not clear how recovery and fork restart occur in higher eukaryotes. Using Xenopus egg extracts, we show that DNA replication continues at a stalled fork through the synthesis and elongation of new primers independent of the checkpoint. This synthesis is dependent on the activity of PCNA, Pol[lowercase Delta] and Pol[Epsilon], and it contributes to the phosphorylation of Chk1. We also used defined DNA structures to show that for a fixed amount of ssDNA, increasing the number of primer-template junctions strongly enhances Chk1 phosphorylation. These results suggest that new primers are synthesized at stalled replication forks by the leading and lagging strand polymerases and that accumulation of these primers may contribute to checkpoint activation.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2010 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Van, Christopher |
|---|---|
| Associated with | Stanford University, Department of Chemical and Systems Biology. |
| Primary advisor | Cimprich, Karlene |
| Thesis advisor | Cimprich, Karlene |
| Thesis advisor | Chen, James Kenneth |
| Thesis advisor | Straight, Aaron, 1966- |
| Thesis advisor | Wang, Teresa |
| Advisor | Chen, James Kenneth |
| Advisor | Straight, Aaron, 1966- |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Christopher Van. |
|---|---|
| Note | Submitted to the Department of Chemical and Systems Biology. |
| Thesis | Ph. D. Stanford University 2010 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2010 by Christopher Van
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