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.

ABSTRACT: Invasive lobular carcinoma of the breast (ILC) is typically estrogen receptor α (ER)-positive and presents with biomarkers of anti-estrogen sensitive disease, yet patients with ILC face particularly poor long-term outcomes with increased recurrence risk, suggesting endocrine response and ER function are unique in ILC. ER is co-regulated by the DNA repair protein Mediator of DNA Damage Checkpoint 1 (MDC1) specifically in ILC cells, driving distinct ER activity. However, this novel MDC1 activity is associated with dysfunctional canonical DNA repair activity by MDC1, but without typical features of DNA repair deficiency. To understand reciprocal activities of MDC1, we profiled the MDC1 interactome and found MDC1-associated proteins in ILC cells mirror a "BRCA-like" state lacking key homologou

SUBMITTER: Sottnik JL 

PROVIDER: S-EPMC11642799 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature