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Rabbit Anti-MDC1/FITC Conjugated antibody
background:
The protein encoded by this gene contains an N-terminal forkhead domain, two BRCA1 SLCterminal (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].
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 H2AFX. 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.
Subunit:
Interacts with several proteins involved in the DNA damage response, although not all these interactions may be direct. Interacts with H2AFX, which requires phosphorylation of H2AFX on 'Ser-139'. Interacts with the MRN complex, composed of MRE11A/MRE11, RAD50, and NBN. Interacts with CHEK2, which requires ATM-mediated phosphorylation of 'Thr-68' within the FHA domain of CHEK2. Interacts constitutively with the BRCA1-BARD1 complex, SMC1A and TP53BP1. Interacts with ATM and FANCD2, and these interactions are reduced upon DNA damage. Also interacts with the PRKDC complex, composed of XRCC6/KU70, XRCC5/KU80 and PRKDC/XRCC7. This interaction may be required for PRKDC autophosphorylation, which is essential for DNA double strand break (DSB) repair. When phosphorylated by ATM, interacts with RNF8 (via FHA domain). Interacts with CEP164. When phosphorylated, interacts with APTX (via FHA-like domain).
Subcellular Location:
Nucleus. Note=Associated with chromatin. Relocalizes to discrete nuclear foci following DNA damage, this requires 'Ser-139' phosphorylation of H2AFX. Colocalizes with APTX at sites of DNA double-strand breaks.
Tissue Specificity:
Highly expressed in testis.
Post-translational modifications:
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.
Similarity:
Contains 2 BRCT domains.
Contains 1 FHA domain.
Database links:
Entrez Gene: 9656 Human
Entrez Gene: 48087 Mouse
GenBank: NP_055456 Human
Omim: 607593 Human
SwissProt: Q14676 Human
SwissProt: Q5PSV9 Mouse
Unigene: 433653 Human
Unigene: 653495 Human
Unigene: 218511 Mouse
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
NFBD1又称MDC1（mediator of DNA damagecheckpoint protein 1）是一个参与DNA损伤细胞应答通路的重要传递和修复因子,在DNA损伤关卡、DNA损伤修复、细胞生长增殖及肿瘤发生中均有作用。
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