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FLASH GENE
Symbol MDC1 contributors: mct - updated : 09-05-2014
HGNC name mediator of DNA damage checkpoint 1
HGNC id 21163
Location 6p21.33      Physical location : 1.960.516 - 30.685.458
Synonym name
  • nuclear factor with BRCT domains protein 1
  • homologue to Drosophila photoreceptor protein calphotin
  • Synonym symbol(s) NFBD1, KIAA0170, Em:AB023051.5, MGC166888, DKFZp781A0122, MDMDC1
    DNA
    TYPE functioning gene
    STRUCTURE 17.87 kb     15 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    TRIM39 6p21.3 tripartite motif-containing 39 C6orf135 6p21.32 chromosome 6 open reading frame 135 MICC 6p21.3 MHC class I polypeptide-related sequence C LOC346173 6p21.32 similar to Succinyl-CoA ligase [ADP-forming] beta-chain, mitochondrial precursor (Succinyl-CoA synthetase, betaA chain) (SCS-betaA) (ATP-specific succinyl-CoA synthetase beta subunit) RANP1 6p21.32 RAN, member RAS oncogene family pseudogene 1 HLA-E 6p21.3 major histocompatibility complex, class I, E GNL1 6p21.3 guanine nucleotide binding protein-like 1 PRR3 6p21.32 proline-rich polypeptide 3 ABCF1 6p21.33 ATP-binding cassette, sub-family F (GCN20), member 1 PPP1R10 6p21.3 protein phosphatase 1, regulatory subunit 10 MRPS18B 6p21.3 mitochondrial ribosomal protein S18B C6orf134 6p21.32 chromosome 6 open reading frame 134 C6orf136 6p21.32 chromosome 6 open reading frame 136 DHX16 6p21.3 DEAH (Asp-Glu-Ala-His) box polypeptide 16 KIAA1949 6p21.3 KIAA1949 protein NRM 6p21.31 nurim (nuclear envelope membrane protein) MDC1 6pter-p21.3 mediator of DNA damage checkpoint 1 OK/SW-cl.56 6p21.32 beta 5-tubulin FLOT1 6p21.3 flotillin 1 IER3 6p21.3 immediate early response 3 DDR1 6p21.3 discoidin domain receptor family, member 1 VARS2L 6p21.33 valyl-tRNA synthetase 2-like GTF2H4 6p21.3 general transcription factor IIH, polypeptide 4, 52kDa LOC389376 6 similar to GSGL541 DPCR1 6p21.32 similar to GSGL541
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    15 - 7385 - 2089 - 2009 19826003
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineparathyroid   highly
    Reproductivefemale systemuteruscervix highly
    Respiratoryrespiratory tractlarynx  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period
    cell cycle     cell cycle, G2M
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminal 197AA with nuclear targeting signal, forkhead-associated (FHA) domain, interacting with activated ATM, CHEK2, and RAD51
  • several repeated motifs, including the Ser-Asp-Thr (SDT), Thr-Gln-X-Phe (TQXF), and Pro-Ser-Thr (PST) motifs
  • a C-terminal tandem BRCT domain
  • HOMOLOGY
    interspecies homolog to Drosophila calphotin
    Homologene
    FAMILY
  • BRCT superfamily
  • CATEGORY adaptor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • being a nuclear transcriptional transactivator contributing to cell growth control
  • playing an important role in checkpoint activation and DNA repair
  • having a role in checkpoint regulation, and executing part of this role by binding the APC/C
  • functioning as an adaptor protein, recruiting different proteins that have a role in the DNA damage response to the transducer kinases and to sites of DNA damage and, thus, facilitating the signal transduction after DNA damage
  • contributing to the early cellular responses to DNA damage
  • playing an important role in the decision of cell survival and death after DNA damage through the regulation of p53
  • functions primarily in homologous recombination/sister chromatid recombination, in a manner strictly dependent upon its ability to interact with gamma-H2AFX but, unexpectedly, not requiring recruitment of TP53BP1 or BRCA1 to gamma-H2AFX chromatin
  • with others ATM signalling mediator proteins, RNF8, RNF168 and TP53BP1 are also required for heterochromatic DSB repair
  • required for focus formation by TP53BP1
  • having a role during mitosis or in the mitotic spindle assembly checkpoint
  • functionally regulates the normal metaphase-to-anaphase transition by modulating the CDC20-dependent activation of the anaphase-promoting complex/cyclosome (APC/C) anaphase-promoting complex/cyclosome (APC/C)
  • in addition to DNA damage response, plays a critical role in the regulation of G2/M transition
  • has a pivotal role in the regulation of proper mitotic entry
  • might contribute to the proper G2/M transition as well as M-phase progression
  • directs chromosome-wide silencing of the sex chromosomes in male germ cells
  • oligomerization of MDC1 plays an important role in DNA damage response (DDR) and help understand the formation of proteins complexes at the sites of DNA damage
  • has a central role in repair of DNA double-strand breaks (DSBs) by both homologous recombination and nonhomologous end joining
  • CELLULAR PROCESS cell life, antiapoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    pathway involving H2AFX–MDC1–WHSC1 regulates the induction of H4K20 methylation on histones around DSBs, which, in turn, facilitates TP53BP1 recruitment
    a component
  • essential component of the cellular response to DNA double strand breaks
  • function in regulating the metaphase-to-anaphase transition
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • GAL4 DNA binding domain
  • directly binds phosphorylated histone H2AFX to regulate cellular responses to DNA double-strand breaks
  • interact with TP53BP1 directly through its tandem BRCT domain and AAs 1288–1409 of TP53BP1 (interaction playing a role in the regulation of mitosis)
  • binds the anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase that controls the cell cycle
  • binds to NBN and targets NBN to the sites of DNA damage(interaction required for proper control of the intra-S-phase checkpoint)
  • interacting with RNF8 (RNF8 is targeted to damaged DNA through an interaction with the double-strand break (DSB)-DDR scaffold protein MDC1, establishing a novel function for MDC1)
  • bound to the N-terminal transactivation domain of TP53 and thereby inhibiting ATM-mediated phosphorylation of TP53 at Ser-15 in the early phase of DNA damage response
  • interacting with UIMC1 (role for the MDC1-UIMC1 interaction in focus formation by the UIMC1-BRCA1 complex
  • JMJDC1 bound to RNF8 and MDC1, and demethylated MDC1 at Lys45, thereby promoting MDC1-RNF8 interaction, RNF8-dependent MDC1 ubiquitylation and recruitment of RAP80-BRCA1 to polyubiquitylated MDC1
  • JMJD1C demethylates MDC1 to regulate the RNF8 and BRCA1-mediated chromatin response to DNA breaks
  • BRCA1 (FANCS), MDC1, and RNF8 are required for BRCA2 (FANCD1) and SLX4 (FANCP) accumulation on the sex chromosomes during meiosis
  • cell & other
    REGULATION
    Phosphorylated by ATM, (ATM phosphorylates MDC1 at Thr-98 following DNA damage, which promotes its oligomerization)
    Other its function is regulated by post-translational phosphorylation, ubiquitylation and sumoylation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    results in a mitotic arrest at metaphase, which is characterized by reduced cellular anaphase-promoting complex/cyclosome activity that is independent of the DNA damage and spindle assembly checkpoint pathways
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    Nfbd1-deficient mice displayed chromosome instability, DNA repair defects and radiation sensitivity