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GoPubMed Proteins lists recent and important papers and reviews for proteins. Page last changed on 19 Aug 2016.

Mediator of DNA-damage checkpoint 1

MDC1, NFBD1, KIAA0170
The protein encoded by this gene contains an N-terminal forkhead domain, two BRCA1 C-terminal (BRCT) motifs and a central domain with 13 repetitions 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. [provided by RefSeq, Jul 2008] (from NCBI)
Top mentioned proteins: H2A, Atm, 53BP1, Iris, Histone
Papers on MDC1
Identification of cell-specific targets of sumoylation during mouse spermatogenesis.
New
Vigodner et al., Charlottesville, United States. In Reproduction, Feb 2016
Furthermore, several proteins that were previously identified as SUMO targets in somatic cells (KAP1 and MDC1) were identified as SUMO targets in germ cells.
Genomic landscape of liposarcoma.
New
Koeffler et al., Singapore, Singapore. In Oncotarget, Jan 2016
Significantly and recurrently mutated genes (false discovery rate < 0.05) included PLEC (27%), MXRA5 (21%), FAT3 (24%), NF1 (20%), MDC1 (10%), TP53 (7%) and CHEK2 (6%).
Expression of potential biomarkers associated with homologous recombination repair in patients with ovarian or triple-negative breast cancer.
New
Yin et al., Tokyo, Japan. In Cancer Biomark, Dec 2015
METHODS: Immunohistochemistry was used to analyse expression of key HR pathway proteins (ATM, ATR, BRCA1, MDC1, MRE11) and PARP-1 in 100 serous ovarian cancer (SOC) and 100 triple-negative breast cancer (TNBC) tumour samples from Japanese patients.
Profiling of primary peripheral blood- and monocyte-derived dendritic cells using monoclonal antibodies from the HLDA10 Workshop in Wollongong, Australia.
New
Bühring et al., Tübingen, Germany. In Clin Transl Immunology, Nov 2015
Mainly three phenotypically and functionally distinct DC subsets are described in the human peripheral blood (PB): plasmacytoid DCs (pDCs), which express the key marker CD303 (BDCA-2), and two myeloid DC subsets (CD1c(+) DC (mDC1) and CD141(+) DC (mDC2)), which express the key markers CD1c (BDCA-1) and CD141 (BDCA-3), respectively.
The proximity ligation assay reveals that at DNA double-strand breaks WRAP53β associates with γH2AX and controls interactions between RNF8 and MDC1.
New
Farnebo et al., Cocos Islands. In Nucleus, Oct 2015
Moreover, formation of complexes between MDC1 and both its partners RNF8 and phosphorylated ATM was visualized.
REV7 counteracts DNA double-strand break resection and affects PARP inhibition.
New
Impact
Rottenberg et al., Amsterdam, Netherlands. In Nature, Jun 2015
REV7 is recruited to DSBs in a manner dependent on the H2AX-MDC1-RNF8-RNF168-53BP1 chromatin pathway, and seems to block HR and promote end joining in addition to its regulatory role in DNA damage tolerance.
The UBC Domain Is Required for BRUCE to Promote BRIT1/MCPH1 Function in DSB Signaling and Repair Post Formation of BRUCE-USP8-BRIT1 Complex.
Du et al., Cincinnati, United States. In Plos One, 2014
This leads to impaired chromatin relaxation, decreased accumulation of MDC1, NBS1, pATM and RAD51 at DSB, and compromised homologous recombination repair of DNA DSB.
Phospho-Ser/Thr-binding domains: navigating the cell cycle and DNA damage response.
Review
Impact
Yaffe et al., Cambridge, United States. In Nat Rev Mol Cell Biol, 2013
Such domains include 14-3-3 proteins, WW domains, Polo-box domains (in PLK1), WD40 repeats (including those in the E3 ligase SCF(βTrCP)), BRCT domains (including those in BRCA1) and FHA domains (such as in CHK2 and MDC1).
Brc1 links replication stress response and centromere function.
Review
Russell et al., Los Angeles, United States. In Cell Cycle, 2013
This compact arrangement of localization domains may be a shared feature of other γH2A-binding proteins, including Rtt107, PTIP and Mdc1.
Sex chromosome inactivation in germ cells: emerging roles of DNA damage response pathways.
Review
Namekawa et al., Cincinnati, United States. In Cell Mol Life Sci, 2012
The trigger of chromosome-wide silencing is activation of the DNA damage response (DDR) pathway, which is centered on the mediator of DNA damage checkpoint 1 (MDC1), a binding partner of phosphorylated histone H2AX (γH2AX).
Sumoylation of MDC1 is important for proper DNA damage response.
GeneRIF
Lou et al., Shanghai, China. In Embo J, 2012
It was shown that MDC1 is sumoylated after DNA damage, and sumoylation of MDC1 at Lys1840 is needed for MDC1 degradation and removal of MDC1 and 53BP1 from DNA damage sites. Sumoylated MDC1 was ubiquitinated by the SUMO-targeted E3 ubiquitin ligase RNF4.
The molecular basis of ATM-dependent dimerization of the Mdc1 DNA damage checkpoint mediator.
GeneRIF
Smerdon et al., Zürich, Switzerland. In Nucleic Acids Res, 2012
A major binding target of the Mdc1 FHA domain is a previously unidentified DNA damage and ATM-dependent phosphorylation site near the N-terminus of Mdc1 itself.
Dimerization, but not phosphothreonine binding, is conserved between the forkhead-associated domains of Drosophila MU2 and human MDC1.
GeneRIF
Ye et al., Beijing, China. In Febs Lett, 2012
As compared to the MDC1 forkhead-associated FHA) domain, the MU2 FHA domain dimerizes using a different and more stable interface and contains a degenerate phosphothreonine-binding pocket.
Structural delineation of MDC1-FHA domain binding with CHK2-pThr68.
GeneRIF
Tsai et al., Taipei, Taiwan. In Biochemistry, 2012
structural insight into MDC1-CHK2 interaction
Recruitment of proteins to DNA double-strand breaks: MDC1 directly recruits RAP80.
GeneRIF
Goldberg et al., Jerusalem, Israel. In Cell Cycle, 2011
MDC1 is required for the recruitment of RAP80 to DNA double-strand breaks.
MMSET regulates histone H4K20 methylation and 53BP1 accumulation at DNA damage sites.
Impact
Lou et al., Rochester, United States. In Nature, 2011
Furthermore, we found that the recruitment of MMSET to DSBs requires the γH2AX-MDC1 pathway; specifically, the interaction between the MDC1 BRCT domain and phosphorylated Ser 102 of MMSET.
The influence of heterochromatin on DNA double strand break repair: Getting the strong, silent type to relax.
Review
Lobrich et al., Burgess Hill, United Kingdom. In Dna Repair (amst), 2011
In contrast, ∼15% of radiation-induced DSBs are repaired with markedly slower kinetics via a process that requires ATM and those mediator proteins, such as MDC1 or 53BP1, that accumulate at ionising radiation induced foci (IRIF).
The cellular response to DNA damage: a focus on MDC1 and its interacting proteins.
Review
Goldberg et al., Jerusalem, Israel. In Nucleus, 2010
Mediator of DNA Damage Checkpoint 1 (MDC1) plays an early and important role in the DDR.
53BP1-dependent robust localized KAP-1 phosphorylation is essential for heterochromatic DNA double-strand break repair.
Impact
GeneRIF
Goodarzi et al., Burgess Hill, United Kingdom. In Nat Cell Biol, 2010
Data show that the ATM signalling mediator proteins MDC1, RNF8, RNF168 and 53BP1 are also required for heterochromatic DSB repair.
Mammalian SUMO E3-ligases PIAS1 and PIAS4 promote responses to DNA double-strand breaks.
Impact
Jackson et al., Cambridge, United Kingdom. In Nature, 2010
These then trigger histone H2AX (also known as H2AFX) phosphorylation and the accumulation of proteins such as MDC1, 53BP1 (also known as TP53BP1), BRCA1, CtIP (also known as RBBP8), RNF8 and RNF168/RIDDLIN into ionizing radiation-induced foci (IRIF) that amplify DSB signalling and promote DSB repair.
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