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

Gene ID: 240087, updated on 21-Apr-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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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
  • 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. 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
  2. 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
  3. Specific association of mouse MDC1/NFBD1 with NBS1 at sites of DNA-damage. Lee AC, et al. Cell Cycle, 2005 Jan. PMID 15611643
  4. Silencing NFBD1/MDC1 enhances the radiosensitivity of human nasopharyngeal cancer CNE1 cells and results in tumor growth inhibition. Wang Z, et al. Cell Death Dis, 2015 Aug 6. PMID 26247734, Free PMC Article
  5. BAZ1B is dispensable for H2AX phosphorylation on Tyrosine 142 during spermatogenesis. Broering TJ, et al. Biol Open, 2015 May 15. PMID 25979708, Free PMC Article

See all (57) 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 histone reader activity ISO
Inferred from Sequence Orthology
more info
  
Process Evidence Code Pubs
involved_in DNA damage response ISO
Inferred from Sequence Orthology
more info
  
acts_upstream_of_or_within DNA repair IEA
Inferred from Electronic Annotation
more info
  
involved_in DNA replication checkpoint signaling ISO
Inferred from Sequence Orthology
more info
  
acts_upstream_of_or_within cell cycle 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
  
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
  

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

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