Accession Number : ADA570974


Title :   Characterization of RACK7 as a Novel Factor Involved in BRCA1 Mutation Mediated Breast Cancer


Descriptive Note : Final rept. 15 Sep 2010-14 Sep 2012


Corporate Author : SALK INST FOR BIOLOGICAL STUDIES LA JOLLA CA


Personal Author(s) : Verma, Inder M ; Zhu, Quan ; Preyer, Martin ; Rommel, Amy


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a570974.pdf


Report Date : Oct 2012


Pagination or Media Count : 72


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.


Descriptors :   *BREAST CANCER , *MUTATIONS , CELLS(BIOLOGY) , CHROMATIN , DEOXYRIBONUCLEIC ACIDS , GENE EXPRESSION , GENES , IN VIVO ANALYSIS , NEOPLASMS , PEPTIDES , PHOSPHORUS TRANSFERASES , PHOSPHORYLATION , PROTEINS , RECEPTOR SITES(PHYSIOLOGY)


Subject Categories : Genetic Engineering and Molecular Biology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE