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    Mdc1 mediator of DNA damage checkpoint 1 [ Mus musculus (house mouse) ]

    Gene ID: 240087, updated on 2-Nov-2024

    Summary

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    Official Symbol
    Mdc1provided by MGI
    Official Full Name
    mediator of DNA damage checkpoint 1provided by MGI
    Primary source
    MGI:MGI:3525201
    See related
    Ensembl:ENSMUSG00000061607 AllianceGenome:MGI:3525201
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Mus musculus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
    Also known as
    Nfbd1; mKIAA0170; 6820401C03
    Summary
    The protein encoded by this gene contains an N-terminal forkhead domain, two BRCA1 C-terminal (BRCT) motifs and a central domain with 7 divergent copies of an approximately 41-amino acid sequence. The encoded protein is required to activate the intra-S phase and G2/M phase cell cycle checkpoints in response to DNA damage. This nuclear protein interacts with phosphorylated histone H2AX near sites of DNA double-strand breaks through its BRCT motifs, and facilitates recruitment of the ATM kinase and meiotic recombination 11 protein complex to DNA damage foci. Mice with mutations in this gene exhibit growth retardation, male infertility, immune defects, chromosome instability, DNA repair defects, and radiation sensitivity. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in testis adult (RPKM 20.0), CNS E11.5 (RPKM 9.8) and 25 other tissues See more
    Orthologs
    human all
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    Genomic context

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    See Mdc1 in Genome Data Viewer
    Location:
    17 B1; 17 18.7 cM
    Exon count:
    17
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) 17 NC_000083.7 (36152390..36170562)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 17 NC_000083.6 (35841495..35859670)

    Chromosome 17 - NC_000083.7Genomic Context describing neighboring genes Neighboring gene flotillin 1 Neighboring gene STARR-seq mESC enhancer starr_42478 Neighboring gene tubulin, beta 5 class I Neighboring gene STARR-positive B cell enhancer ABC_E5607 Neighboring gene STARR-seq mESC enhancer starr_42479 Neighboring gene nurim (nuclear envelope membrane protein) Neighboring gene STARR-seq mESC enhancer starr_42480 Neighboring gene protein phosphatase 1, regulatory subunit 18

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Mouse ENCODE transcriptome data Mouse ENCODE transcriptome data
    • Description: RNA profiling data sets generated by the Mouse ENCODE project.
    • BioProject: PRJNA66167
    • Publication: PMID 25409824
    • Analysis date: n/a

    Bibliography

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    Related articles in PubMed

    1. Specific association of mouse MDC1/NFBD1 with NBS1 at sites of DNA-damage. Lee AC, et al. Cell Cycle, 2005 Jan. PMID 15611643
    2. DNA Damage Response-Independent Role for MDC1 in Maintaining Genomic Stability. Li Z, et al. Mol Cell Biol, 2017 May 1. PMID 28193847, Free PMC Article
    3. Oligomerization of MDC1 protein is important for proper DNA damage response. Luo K, et al. J Biol Chem, 2011 Aug 12. PMID 21705321, Free PMC Article
    4. MDC1 accelerates nonhomologous end-joining of dysfunctional telomeres. Dimitrova N, et al. Genes Dev, 2006 Dec 1. PMID 17158742, Free PMC Article
    5. Distinct roles of chromatin-associated proteins MDC1 and 53BP1 in mammalian double-strand break repair. Xie A, et al. Mol Cell, 2007 Dec 28. PMID 18158901, Free PMC Article

    See all (59) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Oocytes can repair DNA damage during meiosis via a microtubule-dependent recruitment of CIP2A-MDC1-TOPBP1 complex from spindle pole to chromosomes.
      Title: Oocytes can repair DNA damage during meiosis via a microtubule-dependent recruitment of CIP2A-MDC1-TOPBP1 complex from spindle pole to chromosomes.
    2. Mdc1 was dispensable for the synapsis of the autosomes and played only a minor role in X-Y synapsis, compared with the action of H2afx.
      Title: H2AFX and MDC1 promote maintenance of genomic integrity in male germ cells.
    3. Low MDC1 expression promotes invasion and metastasis of pancreatic ductal adenocarcinoma.
      Title: SOX9 activity is induced by oncogenic Kras to affect MDC1 and MCMs expression in pancreatic cancer.
    4. MDC1 plays a fundamentally significant role in maintenance of genomic stability through a DNA damage response-independent pathway.
      Title: DNA Damage Response-Independent Role for MDC1 in Maintaining Genomic Stability.
    5. MDC1 silencing enhances the radiosensitivity of human nasopharyngeal cancer CNE1 cells and results in xenograft tumor growth inhibition.
      Title: Silencing NFBD1/MDC1 enhances the radiosensitivity of human nasopharyngeal cancer CNE1 cells and results in tumor growth inhibition.
    6. oligomerization of MDC1 plays an important role in DDR and help understand the formation of proteins complexes at the sites of DNA damage.
      Title: Oligomerization of MDC1 protein is important for proper DNA damage response.
    7. structural insight into MDC1-CHK2 interaction
      Title: Structural delineation of MDC1-FHA domain binding with CHK2-pThr68.
    8. the DNA damage response pathway centered on MDC1 triggers epigenetic silencing of sex chromosomes in germ cells
      Title: MDC1 directs chromosome-wide silencing of the sex chromosomes in male germ cells.
    9. Data show that loss of Mof leads to reduction of histone H4 K16 acetylation, cell cycle arrest, chromosome aberration, defects in DNA damage repair, and complete loss of Mdc1 response to DNA damage.
      Title: MOF and H4 K16 acetylation play important roles in DNA damage repair by modulating recruitment of DNA damage repair protein Mdc1.
    10. Data show that ATM-dependent resection at a subset of DSBs leads to ATR-dependent Chk1 activation, and that 53BP1(-/-) and MDC1(-/-) cells manifest a checkpoint defect at high radiation doses.
      Title: Role of ATM and the damage response mediator proteins 53BP1 and MDC1 in the maintenance of G(2)/M checkpoint arrest.
    Submit: New GeneRIF Correction See all GeneRIFs (18)

    Variation

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    Alleles

    Alleles of this type are documented at Mouse Genome Informatics  (MGI)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by MGI

    Function Evidence Code Pubs
    enables chromatin-protein adaptor activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables chromatin-protein adaptor activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables histone reader activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables histone reader activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Process Evidence Code Pubs
    involved_in DNA damage response ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in DNA repair IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in DNA replication checkpoint signaling ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in DNA replication checkpoint signaling ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in chromatin organization IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of transcription initiation by RNA polymerase II IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein localization to site of double-strand break ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in protein localization to site of double-strand break ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    located_in chromosome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in focal adhesion ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in nuclear body ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in nucleoplasm ISO
    Inferred from Sequence Orthology
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleus ISO
    Inferred from Sequence Orthology
    more info
    		 PubMed 
    is_active_in site of double-strand break ISO
    Inferred from Sequence Orthology
    more info
    		  
    is_active_in site of double-strand break ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  

    General protein information

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    Preferred Names
    mediator of DNA damage checkpoint protein 1
    Names
    mediation of DNA damage checkpoint 1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001010833.2 → NP_001010833.2  mediator of DNA damage checkpoint protein 1 isoform a

      See identical proteins and their annotated locations for NP_001010833.2

      Status: REVIEWED

      Source sequence(s)
      AK033009, BC085140, BC094363, BY022698, CR974451
      Consensus CDS
      CCDS37604.1
      UniProtKB/Swiss-Prot
      Q52KG1, Q5PSV9, Q5U4D3, Q6ZQH7
      UniProtKB/TrEMBL
      E9QK89
      Related
      ENSMUSP00000080949.7, ENSMUST00000082337.13
      Conserved Domains (4) summary
      PHA03247
      Location:952 → 1429
      PHA03247; large tegument protein UL36; Provisional
      cd17744
      Location:1512 → 1582
      BRCT_MDC1_rpt1; first BRCT domain of mediator of DNA damage checkpoint protein 1 (MDC1) and similar proteins
      cd18441
      Location:1614 → 1693
      BRCT_MDC1_rpt2; second BRCT domain of mediator of DNA damage checkpoint protein 1 (MDC1) and similar proteins
      pfam00498
      Location:55 → 110
      FHA; FHA domain

    2. NM_001405521.1 → NP_001392450.1  mediator of DNA damage checkpoint protein 1 isoform a

      Status: REVIEWED

      Source sequence(s)
      CR974451
      UniProtKB/TrEMBL
      E9QK89

    3. NM_001405522.1 → NP_001392451.1  mediator of DNA damage checkpoint protein 1 isoform a

      Status: REVIEWED

      Source sequence(s)
      CR974451
      UniProtKB/TrEMBL
      E9QK89

    4. NM_001405523.1 → NP_001392452.1  mediator of DNA damage checkpoint protein 1 isoform b

      Status: REVIEWED

      Source sequence(s)
      CR974451

    5. NM_001405524.1 → NP_001392453.1  mediator of DNA damage checkpoint protein 1 isoform b

      Status: REVIEWED

      Source sequence(s)
      CR974451

    6. NM_001405525.1 → NP_001392454.1  mediator of DNA damage checkpoint protein 1 isoform b

      Status: REVIEWED

      Source sequence(s)
      CR974451

    7. NM_001405526.1 → NP_001392455.1  mediator of DNA damage checkpoint protein 1 isoform c

      Status: REVIEWED

      Source sequence(s)
      CR974451

    8. NM_001405527.1 → NP_001392456.1  mediator of DNA damage checkpoint protein 1 isoform d

      Status: REVIEWED

      Source sequence(s)
      CR974451

    9. NM_001405528.1 → NP_001392457.1  mediator of DNA damage checkpoint protein 1 isoform d

      Status: REVIEWED

      Source sequence(s)
      CR974451

    10. NM_001405529.1 → NP_001392458.1  mediator of DNA damage checkpoint protein 1 isoform d

      Status: REVIEWED

      Source sequence(s)
      CR974451

    RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCm39 C57BL/6J

    Genomic

    1. NC_000083.7 Reference GRCm39 C57BL/6J

      Range
      36152390..36170562
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q5PSV9.1 GenPept UniProtKB/Swiss-Prot:Q5PSV9

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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