INTS3 controls the hSSB1-mediated DNA damage response.
Human SSB1 (single-stranded binding protein 1 [hSSB1]) was recently identified as a part of the ataxia telangiectasia mutated (ATM) signaling pathway. To investigate hSSB1 function, we performed tandem affinity purifications of hSSB1 mutants mimicking the unphosphorylated and ATM-phosphorylated states. Both hSSB1 mutants copurified a subset of Integrator complex subunits and the uncharacterized protein LOC58493/c9orf80 (henceforth minute INTS3/hSSB-associated element [MISE]). The INTS3-MISE-hSSB1 complex plays a key role in ATM activation and RAD51 recruitment to DNA damage foci during the response to genotoxic stresses. These effects on the DNA damage response are caused by the control of hSSB1 transcription via INTS3, demonstrating a new network controlling hSSB1 function.
Howard Hughes Medical Institute, New York University Cancer Institute, New York University School of Medicine, New York, NY 10016, USA.
Jeffrey R
JR
Skaar
Derek J
DJ
Richard
Anita
A
Saraf
Alfredo
A
Toschi
Emma
E
Bolderson
Laurence
L
Florens
Michael P
MP
Washburn
Kum Kum
KK
Khanna
Michele
M
Pagano
D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000378:metabolism; D007668:Kidney / Q000166:cytology; D024101:Mitochondrial Proteins; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D014162:Transfection
D004268:DNA-Binding Proteins; D005456:Fluorescent Dyes; C543505:INTS3 protein, human; D007211:Indoles; D024101:Mitochondrial Proteins; D034741:RNA, Small Interfering; C504091:NABP2 protein, human; C007293:DAPI