mediator of DNA damage checkpoint protein 1 (nuclear factor with BRCT domains 1, MDC1, KIAA0170, NFBD1)

^[1]

Function

required for checkpoint mediated cell cycle arrest in response to DNA damage within both S phase & G2/M phase of the cell cycle
scaffold for the recruitment of DNA repair & signal transduction proteins to discrete foci of DNA damage marked by Ser-139 phosphorylation of histone H2AFX (putative)
required for downstream events subsequent to the recruitment of proteins to foci of DNA damage (see #2 above)
- phosphorylation & activation of ATM, CHEK1/CHK1 & CHEK2/CHK2/CDS1 kinases
- stabilization of TP53
- apoptosis
ATM & CHEK2 may also be activated independently (from #3 above) by a parallel pathway mediated by TP53BP1
interacts with several proteins involved in the DNA damage response, not all these interactions may be direct
interacts with H2AFX phosphorylated on Ser-139
interacts with the MRN complex
interacts with phosphorylated CHEK2/CHK2/CDS1 (ATM-mediated phosphorylation of Thr-68 within the FHA domain of CHEK2)
interacts constitutively with BRCA1-BARD1 complex, SMC1L1, TP53BP1
interactions with ATM & FANCD2 are diminished upon DNA damage
interacts with the PRKDC complex, may be required for PRKDC autophosphorylation, essential for DNA double strand break repair
phosphorylated on undefined residues upon exposure to ionizing radiation, ultraviolet radiation, & hydroxyurea
phosphorylation in response to ionizing radiation requires ATM, NBN, & possibly CHEK2
phosphorylated during the G2/M phase of cell cycle & during activation of the mitotic spindle checkpoint

* Tandemly repeated BRCT domains are characteristic of proteins involved in DNA damage signaling. In MDC1, these repeats are required for localization to chromatin which flanks sites of DNA damage marked by Ser-139 phosphorylation of H2AFX.

highly expressed in testis