1. ATM activation is impaired in human cells defective in RecQL4 helicase activity
- Author
-
Soon-Young Park, Joon-Kyu Lee, Hyunsup Kim, and Jun-Sub Im
- Subjects
0301 basic medicine ,DNA Replication ,DNA Repair ,DNA damage ,Biophysics ,Cell Cycle Proteins ,Ataxia Telangiectasia Mutated Proteins ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Cell Line, Tumor ,Humans ,DNA Breaks, Double-Stranded ,Molecular Biology ,Checkpoint Kinase 2 ,MRE11 Homologue Protein ,Osteoblasts ,biology ,RecQ Helicases ,Chemistry ,Effector ,Genetic Complementation Test ,DNA replication ,Wild type ,Rothmund-Thomson Syndrome ,Helicase ,Nuclear Proteins ,Cell Biology ,DNA ,G2-M DNA damage checkpoint ,Cell biology ,Acid Anhydride Hydrolases ,DNA-Binding Proteins ,030104 developmental biology ,DNA Repair Enzymes ,Gene Expression Regulation ,030220 oncology & carcinogenesis ,biology.protein ,Tumor Suppressor Protein p53 ,Protein Binding ,Signal Transduction - Abstract
RecQL4 has been shown to be involved in DNA replication and repair, but its role in DNA damage checkpoint pathway has not been reported. Here, we show that RecQL4 plays an important role in the activation of ataxia telangiectasia mutated (ATM)-dependent checkpoint pathway in human cells. Cells depleted with RecQL4 or Rothmund-Thomson syndrome cells showed significant impairment in the activation of ATM and the downstream effector proteins such as checkpoint kinase 2 and p53 after DNA damage. This defect was recovered with the expression of wild type RecQL4 but not any mutant RecQL4 proteins with defective helicase activities. While RecQL4 failed to show any direct interaction with ATM, it stably interacted with the Mre11-Rad50-Nbs1 complex that is essential for the activation of ATM and was localized on the DNA damage foci. Thus, our results suggest that the helicase activity of RecQL4 plays an important role in the activation of ATM-dependent checkpoint pathway against DNA double strand breaks in human cells.
- Published
- 2018