title: 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.
authors.affiliation: Key Laboratory of Arrhythmias, Ministry of Education, and Institute of Medical Genetics, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Kuntian
authors.initials: K
authors.lastname: Luo
authors.forename: Jian
authors.initials: J
authors.lastname: Yuan
authors.forename: Zhenkun
authors.initials: Z
authors.lastname: Lou
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D010766:Phosphorylation / Q000502:physiology / Q000528:radiation effects; D055503:Protein Multimerization / Q000502:physiology* / Q000528:radiation effects; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011836:Radiation Tolerance / Q000235:genetics / Q000528:radiation effects; D011839:Radiation, Ionizing; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C508937:MDC1 protein, mouse; D025521:Tumor Suppressor Proteins; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases