Integrator3, a Partner of Single-stranded DNA-binding Protein 1, Participates in the DNA Damage Response

Feng Zhang,Jiaxue Wu,Xiaochun Yu

doi:10.1074/jbc.m109.039404

Feng Zhang, Jiaxue Wu + Show 1 more

Open Access

https://doi.org/10.1074/jbc.m109.039404

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Abstract

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.

Highlights

Cell cycle at G1, S, or G2 phase [10]
5B, when cells were treated with a control siRNA, their mitotic was raised from 0.1% to 11.3% following I-SceI expression in the population was dramatically reduced after cells treated with control siRNA, suggesting that I-SceI-intreatment with 2 Gy of ionizing radiation (IR), suggesting that the DNA damage-in- duced homologous recombination repair is activated in the duced G2/M checkpoint is activated and blocks the cell cycle at the cells treated with control siRNA
Like single-stranded DNA (ssDNA)-binding protein 1 (SSB1), INT3 relocates to DNA lesions following IR

Summary

Introduction

Cell cycle at G1, S, or G2 phase [10]. In addition, it enhances the efficiency of DNA damage repair by recruiting and stabilizing the DNA repair machinery at the DNA damage sites [11]. Like the RPA complex, SSB1 participates in homologous recombination by facilitating Rad511⁄7ssDNA filament formation and stabilizing Rad51 at the DNA damage sites. Like SSB1, following DNA damage, INT3 relocates to the DNA damage sites and regulates ATR activation.

Results

Conclusion