Cited by 65DNA Repair MechanismsGenomics and Chromatin DynamicsCancer-related Molecular Pathways

Cut5 Is Required for the Binding of Atr and DNA Polymerase α to Genotoxin-damaged Chromatin

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Parrilla-Castellar, Edgardo R., Karnitz, Larry M.·2003·Journal of Biological Chemistry

Abstract

DNA damage triggers the assembly of checkpoint signaling proteins on chromatin that activate the Chk1 signaling pathway and block S-phase progression. Here we show that genotoxin-induced Chk1 activation requires Cut5 (Mus101/TopBP1) in a process that is independent of the role of Cut5 in DNA replication. Analysis of the role of Cut5 in checkpoint activation revealed that it associated with chromatin following DNA damage in a process that required RPA. Additionally, Cut5 was required for the recruitment of Atr, DNA polymerase alpha, and Rad1 but not RPA to chromatin following DNA damage. Taken together, these results demonstrate that Cut5 plays an integral role in the recruitment and assembly of the Chk1 signaling cascade components following DNA damage.

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Crossref · 10.1074/jbc.c300418200

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Authors
Parrilla-Castellar, E. R., & Karnitz, L. M.
Affiliations
Mayo Clinic (US)
Corresponding author
Karnitz, Larry M.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2003-11
Volume
278
Issue
46
Pages
45507-45511
ISSN
0021-9258 (ISSN-L)
OpenAlex
W1988571930
Cited by
65
References
36
Citations by year
2020: 1 · 2019: 1 · 2017: 1 · 2014: 2 · 2013: 1 · 2012: 2
FWCI
3.43
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (1f31ca099940-01)
  • National Cancer Institute (F31 CA99940, T32CA075926)
  • National Institute of General Medical Sciences (R25 GM5525)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords
TopBP1, ATR kinase, DNA polymerase alpha, RAD1, DNA damage checkpoint, RPA, S-phase checkpoint
MeSH terms
Animals, Chromatin, DNA, DNA Damage, DNA Polymerase I, Models, Biological, Mutagens, Protein Kinases, Xenopus, Signal Transduction, S Phase, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Drosophila Proteins, Xenopus Proteins, Ataxia Telangiectasia Mutated Proteins

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