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Your search keyword '"Hariharasudhan, Gurusamy"' showing total 11 results
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10. ID3 regulates the MDC1-mediated DNA damage response in order to maintain genome stability.

Author

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, and Ho Jin You

Subjects
DNA damage, HELIX-loop-helix motifs, IONIZING radiation, DNA repair, DNA replication, GENOMES
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. [ABSTRACT FROM AUTHOR]

Published
2017
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