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  • [Nat Commun.] ID3 regulates the MDC1-mediated DNA damage response in order to maintain genome stability.

    조선대/ 유호진*, 이정희*

  • 출처
    Nat Commun.
  • 등재일
    2017 Oct 12
  • 저널이슈번호
    ;8(1):903. doi: 10.1038/s41467-017-01051-z.
  • 내용

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    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 double-strand 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.MDC1 is a key component of the DNA damage response and interacts with several factors such as γ-H2AX. Here the authors show that MDC1 interacts with ID3, facilitating MDC1 recruitment to sites of damage and repair of breaks. 

     

    Author information

    Lee JH1,2, Park SJ3,4, Hariharasudhan G3, Kim MJ3, Jung SM3, Jeong SY3,5, Chang IY6, Kim C7, Kim E7, Yu J8, Bae S8, You HJ9,10.

    1Laboratory of Genomic Instability and Cancer Therapeutics, Cancer Mutation Research Center, Chosun University School of medicine, Gwangju, 501-759, Republic of Korea. jhlee75@chosun.ac.kr.2Department of Cellular and Molecular Medicine, Chosun University School of medicine, Gwangju, 501-759, Republic of Korea. jhlee75@chosun.ac.kr.3Laboratory of Genomic Instability and Cancer Therapeutics, Cancer Mutation Research Center, Chosun University School of medicine, Gwangju, 501-759, Republic of Korea.4Department of Premedical Sciences, Chosun University School of medicine, Gwangju, 501-759, Republic of Korea.5Department of Cellular and Molecular Medicine, Chosun University School of medicine, Gwangju, 501-759, Republic of Korea.6Department of Anatomy, Chosun University School of medicine, Gwangju, 501-759, Republic of Korea.7College of Pharmacy, Chosun University, 375 Seosuk-dong, Gwangju, 501-759, Republic of Korea.8Department of Chemistry, Hanyang University, Seoul, 04763, Republic of Korea.9Laboratory of Genomic Instability and Cancer Therapeutics, Cancer Mutation Research Center, Chosun University School of medicine, Gwangju, 501-759, Republic of Korea. hjyou@chosun.ac.kr.10Department of Pharmacology, Chosun University School of medicine, Gwangju, 501-759, Republic of Korea. hjyou@chosun.ac.kr. 

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