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Mouse Anti-MDC1 Recombinant Antibody (P2B11) (CBMAB-BR348LY)


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Summary

Host Animal
Mouse
Specificity
Mouse, Human
Clone
P2B11
Antibody Isotype
IgG
Application
IF: 1:1000 dilution, WB: 0.1-0.5 μg/ml

Basic Information

Immunogen
GST-tagged recombinant protein corresponding to mouse MDC1 at and around the N-terminus
Specificity
Mouse, Human
Antibody Isotype
IgG
Application Notes
The COA includes recommended starting dilutions, optimal dilutions should be determined by the end user.

Formulations & Storage [For reference only, actual COA shall prevail!]

Format
liquid
Buffer
50% glycerol
Preservative
0.09% sodium azide
Storage
Store at +4°C short term (1-2 weeks). Aliquot and store at -20°C long term. Avoid repeated freezethaw cycles.

Target

Full Name
Mediator Of DNA Damage Checkpoint 1
Introduction
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]
Entrez Gene ID
Human9656
Mouse240087
UniProt ID
HumanQ14676
MouseQ5PSV9
Function
Required for checkpoint mediated cell cycle arrest in response to DNA damage within both the S phase and G2/M phases of the cell cycle. May serve as a scaffold for the recruitment of DNA repair and signal transduction proteins to discrete foci of DNA damage marked by 'Ser-139' phosphorylation of histone H2AX. Also required for downstream events subsequent to the recruitment of these proteins. These include phosphorylation and activation of the ATM, CHEK1 and CHEK2 kinases, and stabilization of TP53 and apoptosis. ATM and CHEK2 may also be activated independently by a parallel pathway mediated by TP53BP1.
Biological Process
DNA repair Source: UniProtKB-KW
Mitotic intra-S DNA damage checkpoint signaling Source: UniProtKB
Cellular Location
Nucleus
Other locations
Chromosome
Note: Associated with chromatin. Relocalizes to discrete nuclear foci following DNA damage, this requires 'Ser-139' phosphorylation of H2AX. Colocalizes with APTX at sites of DNA double-strand breaks.
PTM
Phosphorylated upon exposure to ionizing radiation (IR), ultraviolet radiation (UV), and hydroxyurea (HU). Phosphorylation in response to IR requires ATM, NBN, and possibly CHEK2. Also phosphorylated during the G2/M phase of the cell cycle and during activation of the mitotic spindle checkpoint. Phosphorylation at Thr-4 by ATM stabilizes and enhances homodimerization via the FHA domain.
Sumoylation at Lys-1840 by PIAS4 following DNA damage promotes ubiquitin-mediated degradation.
Ubiquitinated by RNF4, leading to proteasomal degradation; undergoes 'Lys-48'-linked polyubiquitination.
More Infomation

Sottnik, J. L., Shackleford, M. T., Richer, A. L., Fu, R., Hesselberth, J. R., & Sikora, M. J. (2023). Co-regulator activity of Mediator of DNA Damage Checkpoint 1 (MDC1) is associated with DNA repair dysfunction and PARP inhibitor sensitivity in lobular carcinoma of the breast. bioRxiv, 2023-10.

Choi, S. H., Cho, K., Kim, E. S., & Yoo, H. Y. (2022). Proline-serine-threonine-repeat region of MDC1 mediates Chk1 phosphorylation and the DNA double-strand break repair. The International Journal of Biochemistry & Cell Biology, 143, 106152.

Chou, J., Kaller, M., Jaeckel, S., Rokavec, M., & Hermeking, H. (2022). AP4 suppresses DNA damage, chromosomal instability and senescence via inducing MDC1/Mediator of DNA damage Checkpoint 1 and repressing MIR22HG/miR-22-3p. Molecular Cancer, 21(1), 1-24.

Xie, R., Yan, Z., Jing, J., Wang, Y., Zhang, J., Li, Y., ... & Wu, C. (2022). Functional defects of cancer-associated MDC1 mutations in DNA damage repair. DNA repair, 114, 103330.

Sottnik, J. L., Bordeaux, E. K., Mehrotra, S., Ferrara, S. E., Goodspeed, A. E., Costello, J. C., & Sikora, M. J. (2021). Mediator of DNA damage checkpoint 1 (MDC1) is a novel estrogen receptor coregulator in invasive lobular carcinoma of the breast. Molecular Cancer Research, 19(8), 1270-1282.

Ruff, S. E., Logan, S. K., Garabedian, M. J., & Huang, T. T. (2020). Roles for MDC1 in cancer development and treatment. DNA repair, 95, 102948.

Zhang, X., Hu, F., Liu, L., & Xu, B. (2019). Effect of silencing of mediator of DNA damage checkpoint protein 1 on the growth of oral squamous cell carcinoma in vitro and in vivo. European Journal of Oral Sciences, 127(6), 494-499.

Beck, C., Castañeda-Zegarra, S., Huse, C., Xing, M., & Oksenych, V. (2019). Mediator of DNA damage checkpoint protein 1 facilitates V (D) J recombination in cells lacking DNA repair factor XLF. Biomolecules, 10(1), 60.

Salguero, I., Belotserkovskaya, R., Coates, J., Sczaniecka-Clift, M., Demir, M., Jhujh, S., ... & Jackson, S. P. (2019). MDC1 PST-repeat region promotes histone H2AX-independent chromatin association and DNA damage tolerance. Nature Communications, 10(1), 5191.

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For research use only. Not intended for any clinical use.

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