Endogenous hSNM1B/Apollo interacts with TRF2 and stimulates ATM in response to ionizing radiation.
Human SNM1B/Apollo is involved in the cellular response to DNA-damage, however, its precise role is unknown. Recent reports have implicated hSNM1B in the protection of telomeres. We have found hSNM1B to interact with TRF2, a protein which functions in telomere protection and in an early response to ionizing radiation. Here we show that endogenous hSNM1B forms foci which colocalize at telomeres with TRF1 and TRF2. However, we observed that additional hSNM1B foci could be induced upon exposure to ionizing radiation (IR). In live-cell-imaging experiments, hSNM1B localized to photo-induced double-strand breaks (DSBs) within 10s post-induction. Further supporting a role for hSNM1B in the early stages of the cellular response to DSBs, we observed that autophosphorylation of ATM, as well as the phosphorylation of ATM target proteins in response to IR, was attenuated in cells depleted of hSNM1B. These observations suggest an important role for hSNM1B in the response to IR damage, a role that may be, in part, upstream of the central player in maintenance of genome integrity, ATM.
Demuth
Ilja
I
Institut für Humangenetik, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany. ilja.demuth@charite.de <ilja.demuth@charite.de>
Bradshaw
Paul S
PS
Lindner
Anika
A
Anders
Marco
M
Heinrich
Stefanie
S
Kallenbach
Julia
J
Schmelz
Karin
K
Digweed
Martin
M
Meyn
M Stephen
MS
Concannon
Patrick
P
D064007:Ataxia Telangiectasia Mutated Proteins; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D045643:DNA Repair Enzymes / Q000378:metabolism* / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005090:Exodeoxyribonucleases; D005455:Fluorescent Antibody Technique; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism* / Q000502:physiology; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D034741:RNA, Small Interfering; D011839:Radiation, Ionizing; D035341:Telomeric Repeat Binding Protein 2 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D035341:Telomeric Repeat Binding Protein 2; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; C493741:DCLRE1B protein, human; D005090:Exodeoxyribonucleases; D045643:DNA Repair Enzymes