Characterization of RACK7 as a Novel Factor Involved in BRCA1 Mutation Mediated Breast Cancer
Abstract
Though BRCA1 has been shown to play a role in DNA end resection, likely critical in the cell s decision to undergo homologous recombination or non-homologous end joining repair pathways, much of BRCA1 function remains unknown. To identify genes that cooperate with BRCA1 in DNA damage response and tumor suppression, we performed a lentiviral vector based cDNA library screen. ZMYND8 (zinc finger Mynd-type containing 8), previously Rack7 (receptor for activated C kinase) or Prkcbp1 (protein kinase C binding protein 1), was identified in our screen as a candidate gene that could modulate the DNA damage hypersensitivity in cells lacking BRCA1. Biochemical data indicates that ZMYND8 might be involved in chromatin reorganization surrounding a stalled fork, which may be vital in preventing collapse and granting genomic stability. Overexpression of ZMYND8 in breast, ovarian, and several other malignancies, could be a novel mechanism to overcome replica-tion stress resulting from BRCA1 dysfunction. This suggests that ZMYND8 and BRCA1 could function epistatically, a phenomenon we continue to investigate using our lab-generated mouse models. In conclusion, our novel findings demonstrate that ZMYND8 is required to prevent the reversal of stalled replication forks, and thereby contributes to the preservation genomic stability under replication stress.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2012
- Accession Number
- ADA570974
Entities
People
- Amy Rommel
- Inder M. Verma
- Martin Preyer
- Quan Zhu
Organizations
- Salk Institute for Biological Studies