Single-stranded DNA Induces Ataxia Telangiectasia Mutant (ATM)/p53-dependent DNA Damage and Apoptotic Signals

Single-stranded DNA has been speculated to be the initial signal in the DNA damage signaling pathway. We showed that introduction of single-stranded DNA with diverse sequences into mammalian cells induced DNA damage as well as apoptosis signals. Like DNA damaging agents, single-stranded DNA up-regul...

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Bibliographic Details
Published in:The Journal of biological chemistry 2003-04, Vol.278 (14), p.12475-12481
Main Authors: Nur-E-Kamal, Alam, Li, Tsai-Kun, Zhang, Ailing, Qi, Haiyan, Hars, Eszter S, Liu, Leroy F
Format: Article
Language:English
Subjects:
3T3 Cells
Animals
Apoptosis - genetics
Ataxia Telangiectasia - genetics
Ataxia Telangiectasia Mutated Proteins
Biomarkers
Cell Cycle Proteins
Deoxyribonucleases - metabolism
DNA Damage - physiology
DNA, Single-Stranded - pharmacology
DNA-Binding Proteins
Mice
Mice, Inbred BALB C
Mice, Mutant Strains
Oligonucleotides - pharmacology
Protein-Serine-Threonine Kinases - genetics
Signal Transduction - genetics
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Proteins
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Summary:Single-stranded DNA has been speculated to be the initial signal in the DNA damage signaling pathway. We showed that introduction of single-stranded DNA with diverse sequences into mammalian cells induced DNA damage as well as apoptosis signals. Like DNA damaging agents, single-stranded DNA up-regulated p53 and activated the nuclear kinase ataxia telangiectasia mutant (ATM) as evidenced by phosphorylation of histone 2AX, an endogenous ATM substrate. Single-stranded DNA also triggered apoptosis as evidenced by the formation of caspase-dependent chromosomal DNA strand breaks, cytochrome c release, and increase in reactive oxygen species production. Moreover, single-stranded DNA-induced apoptosis was reduced significantly in p53 null cells and in cells treated with ATM small interfering RNA. These results suggest that single-stranded DNA may act upstream of ATM/p53 in DNA damage signaling.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M212915200