Specific association of mouse MDC1/NFBD1 with NBS1 at sites of DNA-damage.
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.
Lee
Alicia C
AC
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Fernandez-Capetillo
Oscar
O
Pisupati
Venkat
V
Jackson
Stephen P
SP
Nussenzweig
André
A
D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D019457:Chromosome Breakage; D004249:DNA Damage; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D018816:Genes, cdc / Q000502:physiology; D006657:Histones / Q000235:genetics / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000076228:MRE11 Homologue Protein; D008540:Meiosis / Q000235:genetics / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011839:Radiation, Ionizing; D011995:Recombination, Genetic; D034421:Sus scrofa
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D000076228:MRE11 Homologue Protein; D009687:Nuclear Proteins; C508937:MDC1 protein, mouse; C121766:MRE11 protein, human; C512689:Mre11a protein, mouse; C466108:Nijmegen breakage syndrome 1 protein, mouse; C475961:gamma-H2AX protein, mouse