MDC1 Lentiviral Activation Particles (h): sc-405652-LAC

Mediator of DNA damage checkpoint 1 (MDC1) is a nuclear scaffold protein that coordinates the DNA damage response by binding γH2AX at sites of double-strand breaks and amplifying checkpoint signaling. Through recruitment and stabilization of repair and signaling factors including ATM, RNF8/RNF168 ubiquitin ligases, and 53BP1/BRCA1-associated complexes, MDC1 supports chromatin remodeling, damage foci formation, and efficient pathway choice between non-homologous end joining and homologous recombination. MDC1 activity intersects with cell-cycle checkpoint control and genome maintenance programs that protect against replication stress and chromosomal instability. Dysregulation of MDC1-dependent signaling has been linked to impaired DNA repair capacity and genomic instability phenotypes relevant to cancer biology and sensitivity to DNA-damaging stressors.

MDC1 Lentiviral Activation Particles (h) address this need by packaging the complete synergistic activation mediator (SAM) transcriptional activation system into transduction-ready, high-titer lentiviral particles, enabling efficient MDC1 upregulation across a broader range of human cell types.

MDC1 Lentiviral Activation Particles (h) deliver all functional components of the synergistic activation mediator (SAM) system via lentiviral transduction. The system comprises three particle preparations co-transduced into target cells: one encoding catalytically inactive dCas9 (D10A and N863A mutations) fused to the VP64 transactivation domain with a blasticidin resistance gene; one encoding the MS2-p65-HSF1 fusion protein with a hygromycin resistance gene; and one encoding a target-specific 20 nt sgRNA fused to two MS2 RNA aptamers with a puromycin resistance gene. Following lentiviral transduction and genomic integration of the expression cassettes, the SAM components are stably expressed and assemble at the target locus within the proximal promoter region upstream of the MDC1 transcriptional start site, where VP64, p65, and HSF1 act cooperatively to recruit endogenous transcriptional machinery and drive sustained upregulation of endogenous MDC1 expression. The use of nuclease-inactive dCas9 avoids the introduction of double-strand DNA breaks and preserves the native MDC1 genomic locus and regulatory architecture.

The lentiviral format offers several practical advantages: stable genomic integration supports heritable activation across cell divisions; high-titer particle preparations eliminate the need for in-house viral production; and compatibility with primary, non-dividing, and transfection-resistant cell types expands experimental accessibility. Successful transduction can be confirmed and enriched through triple antibiotic selection using puromycin, hygromycin, and blasticidin.

For Research Use Only. Not Intended for Diagnostic or Therapeutic Use.