Journal
CELL CYCLE
Volume 4, Issue 1, Pages 177-182Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.4.1.1354
Keywords
DNA damage response; KIAA0170; NFBD1; MDC1; mediator of DNA damage checkpoint 1; MRN complex
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Funding
- NATIONAL CANCER INSTITUTE [ZIABC010283, Z01BC010283] Funding Source: NIH RePORTER
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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 co-localize with the MRE11-RAD50-NBS1 (MRN) complex and factors such as gammaH2AX 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 co-localize 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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