The structural determinants of checkpoint activation

Here, we demonstrate that primed, single-stranded DNA (ssDNA) is sufficient for activation of the ATR-dependent checkpoint pathway in Xenopus egg extracts. Using this structure, we define the contribution of the 5'- and 3'-primer ends to Chk1 activation when replication is blocked and ongo...

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Bibliographic Details
Published in:Genes & development 2007-04, Vol.21 (8), p.898-903
Main Authors: MacDougall, Christina A, Byun, Tony S, Van, Christopher, Yee, Muh-ching, Cimprich, Karlene A
Format: Article
Language:English
Subjects:
Animals
Ataxia Telangiectasia Mutated Proteins
Cell Cycle
Cell Cycle Proteins - metabolism
Checkpoint Kinase 1
DNA Damage
DNA Replication
DNA, Single-Stranded - metabolism
Ovum - chemistry
Phosphorylation
Protein Kinases - metabolism
Protein-Serine-Threonine Kinases - metabolism
Research Communication
S Phase
Xenopus
Xenopus laevis
Xenopus Proteins - metabolism
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Summary:Here, we demonstrate that primed, single-stranded DNA (ssDNA) is sufficient for activation of the ATR-dependent checkpoint pathway in Xenopus egg extracts. Using this structure, we define the contribution of the 5'- and 3'-primer ends to Chk1 activation when replication is blocked and ongoing. In addition, we show that although ssDNA is not sufficient for checkpoint activation, the amount of ssDNA adjacent to the primer influences the level of Chk1 phosphorylation. These observations define the minimal DNA requirements for checkpoint activation and suggest that primed ssDNA represents a common checkpoint activating-structure formed following many types of damage.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.1522607