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Oligomerization of MDC1 protein is important for proper DNA damage response.

ABSTRACT: Mediator of DNA damage checkpoint 1 (MDC1) plays an important role in the DNA damage response (DDR). MDC1 functions as a mediator protein and binds multiple proteins involved in different aspects of the DDR. However, little is know about the organization of MDC1 complexes. Here we show that ataxia telangiectasia, mutated (ATM) phosphorylates MDC1 at Thr-98 following DNA damage, which promotes its oligomerization. Oligomerization of MDC1 is important for the accumulation of MDC1 complex at the sites of DNA damage. Mutation of Thr-98 (T98A) would abolish its oligomerization and result in a defect in DNA damage checkpoint activation and increased sensitivity to irradiation. Taken together, these results suggest that the oligomerization of MDC1 plays an important role in DDR and help understand the formation of proteins complexes at the sites of DNA damage.

SUBMITTER: Luo K

PROVIDER: S-EPMC3151064 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Oligomerization of MDC1 protein is important for proper DNA damage response.

Luo Kuntian K Yuan Jian J Lou Zhenkun Z

The Journal of biological chemistry 20110624 32

Mediator of DNA damage checkpoint 1 (MDC1) plays an important role in the DNA damage response (DDR). MDC1 functions as a mediator protein and binds multiple proteins involved in different aspects of the DDR. However, little is know about the organization of MDC1 complexes. Here we show that ataxia telangiectasia, mutated (ATM) phosphorylates MDC1 at Thr-98 following DNA damage, which promotes its oligomerization. Oligomerization of MDC1 is important for the accumulation of MDC1 complex at the si ...[more]

PMID: 21705321

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Author Correction: ID3 regulates the MDC1-mediated DNA damage response in order to maintain genome stability.

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