Specific Association of Mouse MDC1/NFBD1 with NBS1 at Sites of DNA-Damage

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Abstract
Human MDC1/NFBD1 has been found to interact with key players of the DNA-damage response machinery. Here, we identify and describe a functional homologue of MDC1/NFBD1 in Mus musculus. The mouse homologue, mMDC1, retains the key motifs identified in the human protein and in response to ionizing radiation forms foci that colocalize with the MRE11-RAD50- NBS1 (MRN) complex and factors such as ?H2AX and 53BP1. In addition, mMDC1 is associated with DNA damage sites generated during meiotic recombination as well as the X and Y chromosomes during the late stages of meiotic prophase I. Finally, whereas MDC1 shows strong colocalization with the MRN complex in response to DNA damage it does not colocalize with the MRN complex on replicating chromatin. These data suggest that mMDC1 is a marker for both exogenously and endogenously generated DNA double-stranded breaks and that its interaction with the MRN complex is initiated exclusively by DNA damage.

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