Specific association of mouse MDC1/NFBD1 with NBS1 at sites of DNA-damage

Alicia C Lee; Oscar Fernandez-Capetillo; Venkat Pisupati; Stephen P Jackson; André Nussenzweig

doi:10.4161/cc.4.1.1354

Specific association of mouse MDC1/NFBD1 with NBS1 at sites of DNA-damage

Cell Cycle. 2005 Jan;4(1):177-82. doi: 10.4161/cc.4.1.1354. Epub 2005 Jan 11.

Authors

Alicia C Lee¹, Oscar Fernandez-Capetillo, Venkat Pisupati, Stephen P Jackson, André Nussenzweig

Affiliation

¹ Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

PMID: 15611643
DOI: 10.4161/cc.4.1.1354

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 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.

Publication types

Comparative Study

MeSH terms

Adaptor Proteins, Signal Transducing
Amino Acid Motifs
Amino Acid Sequence
Animals
Cell Cycle Proteins / genetics
Cell Cycle Proteins / metabolism*
Cell Line
Chromosome Breakage
DNA Damage*
DNA Repair Enzymes
DNA-Binding Proteins / genetics
DNA-Binding Proteins / physiology
Genes, cdc / physiology
Histones / genetics
Histones / physiology
Humans
Intracellular Signaling Peptides and Proteins / chemistry
Intracellular Signaling Peptides and Proteins / genetics
Intracellular Signaling Peptides and Proteins / metabolism*
MRE11 Homologue Protein
Meiosis / genetics
Meiosis / physiology
Mice
Molecular Sequence Data
Nuclear Proteins / genetics
Nuclear Proteins / metabolism*
Radiation, Ionizing
Recombination, Genetic
Sus scrofa

Substances

Adaptor Proteins, Signal Transducing
Cell Cycle Proteins
DNA-Binding Proteins
H2AX protein, mouse
Histones
Intracellular Signaling Peptides and Proteins
MDC1 protein, mouse
MRE11 protein, human
Mre11a protein, mouse
Nijmegen breakage syndrome 1 protein, mouse
Nuclear Proteins
MRE11 Homologue Protein
DNA Repair Enzymes