Abstract B14: A novel role for BRD9 in regulating cellular growth and DNA damage response pathways

We examined if SWI/SNF chromatin remodeling activity was dependent on BRD9 status and how this correlated with the growth phenotype. Nucleosome accessibility was significantly decreased when BRD9 was depleted indicating chromatin exists in a more compacted conformation. However, BRD9 knockdown does not result in alterations in assembly or stability of the SWI/SNF complex. Though loss of BRD9 does not perturb SWI/SNF dynamics, it may be required for complex recruitment to chromatin directly or by tethering through protein-protein interactions. Identification of novel BRD9-interacting proteins that target recruitment was carried out by proteomic survey. Analysis of the study revealed enrichment of proteins involved in DNA damage repair pathways. Using a double strand break reporter, we examined if BRD9 depletion perturbed homology-directed or non-homologous end joining repair pathways. Knockdown of BRD9 increased NHEJ-associated reporter activity but had subtle effect on homology-directed repair events. BRD9 colocalizes with H2AX foci upon damage but this colocalization is lost upon depletion of BRD9.We propose that BRD9 is necessary for recruitment of SWI/SNF to sites of damage, to permit chromatin expansion and assembly of homology-directed repair factors. However, knockdown of BRD9 may shift the balance and favor interactions of non-homologous end joining pathway players to sites of damage, resulting in enhanced error-prone repair and ultimately leading to oncogenic transfor...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: DNA Damage Signaling: Poster Presentations - Proffered Abstracts Source Type: research