Integrator3, a partner of single-stranded DNA-binding protein 1, participates in the DNA damage response.
Single-stranded DNA-binding protein 1 (SSB1) plays an important role in the DNA damage response and maintenance of genomic stability. Here, by using protein affinity purification, we have identified Integrator3 (INT3) as a novel partner of SSB1. INT3 forms a complex with SSB1 by constitutively interacting with SSB1 regardless of DNA damage. However, following DNA damage, along with SSB1, INT3 relocates to the DNA damage sites and regulates the accumulation of TopBP1 and BRCA1 there. Moreover, INT3 controls DNA damage-induced Chk1 activation and G(2)/M checkpoint activation. In addition, INT3 is involved in homologous recombination repair by regulating Rad51 foci formation following DNA damage. Taken together, these results demonstrate that INT3 plays a key role in the DNA damage response.
Zhang
Feng
F
Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Wu
Jiaxue
J
Yu
Xiaochun
X
D019313:BRCA1 Protein / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D051135:Rad51 Recombinase
D019313:BRCA1 Protein; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C543505:INTS3 protein, human; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; C504091:NABP2 protein, human; C110513:TOPBP1 protein, human; C495153:RAD51 protein, human; D051135:Rad51 Recombinase