Domain:Tandemly repeated BRCT domains are characteristic of proteins involved in DNA damage signaling. In MDC1 , these repeats are required for localization to chromatin which flanks sites of DNA damage marked by 'Ser-139' phosphorylation of H2AFX. ,Function:Required for checkpoint mediated cell cycle arrest in response to DNA damage within both the S phase and G2/M phases of the cell cycle. May serve as a scaffold for the recruitment of DNA repair and signal transduction proteins to discrete foci of DNA damage marked by 'Ser-139' phosphorylation of histone H2AFX. Also required for downstream events subsequent to the recruitment of these proteins. These include phosphorylation and activation of the ATM , CHEK1/CHK1 and CHEK2/CHK2/CDS1 kinases , and stabilization of TP53 and apoptosis. ATM and CHEK2 may also be activated independently by a parallel pathway mediated by TP53BP1. ,PTM:Phosphorylated upon exposure to ionizing radiation (IR) , ultraviolet radiation (UV) , and hydroxyurea (HU) . Phosphorylation in response to IR requires ATM , NBN , and possibly CHEK2. Also phosphorylated during the G2/M phase of the cell cycle and during activation of the mitotic spindle checkpoint. ,sequence Caution:Translated as Gln. ,similarity:Contains 1 FHA domain. ,similarity:Contains 2 BRCT domains. ,subcellular location:Associated with chromatin. Relocalizes to discrete nuclear foci following DNA damage , this requires 'Ser-139' phosphorylation of H2AFX. ,subunit:Interacts with several proteins involved in the DNA damage response , although not all these interactions may be direct. Interacts with H2AFX , which requires phosphorylation of H2AFX on 'Ser-139'. Interacts with the MRN complex , composed of MRE11A/MRE11 , RAD50 , and NBN. Interacts with CHEK2/CHK2/CDS1 , which requires ATM-mediated phosphorylation of 'Thr-68' within the FHA domain of CHEK2. Interacts constitutively with the BRCA1-BARD1 complex , SMC1A and TP53BP1. Interacts with ATM and FANCD2 , and these interactions are reduced upon DNA damage. Also interacts with the PRKDC complex , composed of G22P1/KU70 , XRCC5/KU80 and PRKDC/XRCC7. This interaction may be required for PRKDC autophosphorylation , which is essential for DNA double strand break (DSB) repair. When phosphorylated by ATM , interacts with RNF8. Interacts with CEP164. ,tissue specificity:Highly expressed in testis. ,
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