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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Vydané v:Genes & development Ročník 21; číslo 8; s. 898
Hlavní autori: MacDougall, Christina A, Byun, Tony S, Van, Christopher, Yee, Muh-ching, Cimprich, Karlene A
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States 15.04.2007
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Abstract 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.
AbstractList 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.
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.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.
Author MacDougall, Christina A
Cimprich, Karlene A
Byun, Tony S
Yee, Muh-ching
Van, Christopher
Author_xml – sequence: 1
  givenname: Christina A
  surname: MacDougall
  fullname: MacDougall, Christina A
  organization: Department of Chemical and Systems Biology, Stanford University, Stanford, California 94305, USA
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  surname: Yee
  fullname: Yee, Muh-ching
– sequence: 5
  givenname: Karlene A
  surname: Cimprich
  fullname: Cimprich, Karlene A
BackLink https://www.ncbi.nlm.nih.gov/pubmed/17437996$$D View this record in MEDLINE/PubMed
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Snippet Here, we demonstrate that primed, single-stranded DNA (ssDNA) is sufficient for activation of the ATR-dependent checkpoint pathway in Xenopus egg extracts....
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SubjectTerms 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
S Phase
Xenopus laevis
Xenopus Proteins - metabolism
Title The structural determinants of checkpoint activation
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