Cut5 is required for the binding of Atr and DNA polymerase alpha to genotoxin-damaged chromatin.
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.
Parrilla-Castellar
Edgardo R
ER
Tumor Biology Program, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Karnitz
Larry M
LM
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism* / Q000502:physiology*; D002843:Chromatin / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004256:DNA Polymerase I / Q000378:metabolism*; D029721:Drosophila Proteins; D008954:Models, Biological; D009153:Mutagens / Q000378:metabolism / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D016196:S Phase; D015398:Signal Transduction; D014981:Xenopus; D029867:Xenopus Proteins
D018797:Cell Cycle Proteins; D002843:Chromatin; D029721:Drosophila Proteins; D009153:Mutagens; D029867:Xenopus Proteins; C416162:mus101 protein, Drosophila; D004247:DNA; D011494:Protein Kinases; C576898:Atr protein, Xenopus; C102333:histone H1 kinase; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D004256:DNA Polymerase I