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- Title
ID3 regulates the MDC1-mediated DNA damage response in order to maintain genome stability.
- Authors
Jung-Hee Lee; Seon-Joo Park; Hariharasudhan, Gurusamy; Min-Ji Kim; Sung Mi Jung; Seo-Yeon Jeong; In-Youb Chang; Cheolhee Kim; Eunae Kim; Jihyeon Yu; Sangsu Bae; Ho Jin You
- Abstract
MDC1 plays a critical role in the DNA damage response (DDR) by interacting directly with several factors including γ-H2AX. However, the mechanism by which MDC1 is recruited to damaged sites remains elusive. Here, we show that MDC1 interacts with a helix--loop--helix (HLH)-containing protein called inhibitor of DNA-binding 3 (ID3). In response to doublestrand breaks (DSBs) in the genome, ATM phosphorylates ID3 at serine 65 within the HLH motif, and this modification allows a direct interaction with MDC1. Moreover, depletion of ID3 results in impaired formation of ionizing radiation (IR)-induced MDC1 foci, suppression of γ-H2AX-bound MDC1, impaired DSB repair, cellular hypersensitivity to IR, and genomic instability. Disruption of the MDC1--ID3 interaction prevents accumulation of MDC1 at sites of DSBs and suppresses DSB repair. Thus, our study uncovers an ID3-dependent mechanism of recruitment of MDC1 to DNA damage sites and suggests that the ID3--MDC1 interaction is crucial for DDR.
- Subjects
DNA damage; HELIX-loop-helix motifs; IONIZING radiation; DNA repair; DNA replication; GENOMES
- Publication
Nature Communications, 2017, Vol 8, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-017-01051-z