Histone reader protein 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 (      ). Specifically recognizes and binds histone H2AX phosphorylated at 'Ser-139', a marker of DNA damage, serving as a scaffold for the recruitment of DNA repair and signal transduction proteins to discrete foci of DNA damage sites (  ). Also required for downstream events subsequent to the recruitment of these proteins ( , ). These include phosphorylation and activation of the ATM, CHEK1 and CHEK2 kinases, and stabilization of TP53/p53 and apoptosis ( ). ATM and CHEK2 may also be activated independently by a parallel pathway mediated by TP53BP1 ( ). Required for chromosomal stability during mitosis by promoting recruitment of TOPBP1 to DNA double strand breaks (DSBs): TOPBP1 forms filamentous assemblies that bridge MDC1 and tether broken chromosomes during mitosis .
Subcellular locations: Nucleus, Chromosome
Associated with chromatin ( , ). Relocalizes to discrete nuclear foci following DNA damage, this requires 'Ser-139' phosphorylation of H2AX (  , ). Colocalizes with APTX at sites of DNA double-strand breaks .
Highly expressed in testis.