Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1074372 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To validate a high-throughput screening data in human cells using Multiplexed Assays for Variant Effects (MAVE), we performed a high-throughput deep mutational scanning of single nucleotide changes in exon 10 encoding p.G1000 to p.I1037 of the WD40 domain of PALB2 using a cell survival assay in haploid human HAP1 cells. We obtained MAVE scores for 276 single-nucleotide variants, leading to 9 nonsense and 68 synonymous changes, as well as 199 amino acid substitutions. Both variant groups showed an asymmetric distribution that is skewed towards low MAVE scores of nonsense and damaging variants, respectively. These MAVE data included scores for 218 unique single-nucleotide variants, leading to 9 nonsense changes and 209 amino acid substitutions. We observed a good and significant correlation between the outcomes from the MAVE and high-throughput screens (n=179, r=-0,6439, p<0.0001), indicating concordance between the outcomes of high-throughput analysis of PALB2 variants in human and mouse cells.
2024-02-08 | GSE255117 | GEO
Project description:Breast and ovarian cancer susceptibility genes, BRCA1 and PALB2 have enigmatic roles in cellular growth and mammalian development. While these genes are essential for growth during early developmental programs, inactivation later in adulthood leads to increased growth and formation of tumors, leading to their designation as tumor suppressors. We performed genome-wide analysis assessing their chromatin residence and gene expression responsiveness using high throughput sequencing in breast epithelial cells. These experiments revealed a critical role for BRCA1 and PALB2 in transcriptional responsiveness to NF-kB, a crucial mediator of growth and inflammatory response during development and cancer. Importantly, we also uncovered a vital role for these proteins in response to retinoic acid (RA), a growth inhibitory signal in breast cancer cells, which may constitute the basis for their tumor suppressor activity. Comparison of the genome wide profiles of the BRCA protein complex (BRCA1 and PALB2) and phosphorylated RNAPII (P-Ser2) in MCF10A cells by ChIP-seq. Effect of BRCA1 and PALB2 knockdown (shRNAs) on transcription was assessed by RNA-seq.
2013-09-30 | E-GEOD-40591 | biostudies-arrayexpress
Project description:The BRCA1 tumor suppressor gene encodes a multi-domain protein for which several functions have been described. These include a key role in homologous recombination repair (HRR) of DNA double-strand breaks (DSBs), which is shared with two other high-risk hereditary breast cancer suppressors, BRCA2 and PALB2. Although both BRCA1 and BRCA2 interact with PALB2, BRCA1 missense variants affecting its PALB2-interacting coiled-coil domain are considered sequence variants of uncertain clinical significance (VUS). Using genetically engineered mice, we now show that a BRCA1 coiled-coil domain VUS, Brca1 p.L1363P, disrupting the interaction with PALB2 leads to embryonic lethality and loss of breast cancer suppression. Brca1 p.L1363P mammary tumors develop with a similar latency as Brca1-null tumors, but show different histopathological features and more stable DNA copy number profiles. Nevertheless, Brca1 p.L1363P mammary tumors are HRR-incompetent and responsive to cisplatin and PARP inhibition.
2022-02-01 | GSE182449 | GEO
Project description:The BRCA1 tumor suppressor gene encodes a multi-domain protein for which several functions have been described. These include a key role in homologous recombination repair (HRR) of DNA double-strand breaks (DSBs), which is shared with two other high-risk hereditary breast cancer suppressors, BRCA2 and PALB2. Although both BRCA1 and BRCA2 interact with PALB2, BRCA1 missense variants affecting its PALB2-interacting coiled-coil domain are considered sequence variants of uncertain clinical significance (VUS). Using genetically engineered mice, we now show that a BRCA1 coiled-coil domain VUS, Brca1 p.L1363P, disrupting the interaction with PALB2 leads to embryonic lethality and loss of breast cancer suppression. Brca1 p.L1363P mammary tumors develop with a similar latency as Brca1-null tumors, but show different histopathological features and more stable DNA copy number profiles. Nevertheless, Brca1 p.L1363P mammary tumors are HRR-incompetent and responsive to cisplatin and PARP inhibition.
2022-02-01 | GSE182448 | GEO
Project description:Breast and ovarian cancer susceptibility genes, BRCA1 and PALB2 have enigmatic roles in cellular growth and mammalian development. While these genes are essential for growth during early developmental programs, inactivation later in adulthood leads to increased growth and formation of tumors, leading to their designation as tumor suppressors. We performed genome-wide analysis assessing their chromatin residence and gene expression responsiveness using high throughput sequencing in breast epithelial cells. These experiments revealed a critical role for BRCA1 and PALB2 in transcriptional responsiveness to NF-kB, a crucial mediator of growth and inflammatory response during development and cancer. Importantly, we also uncovered a vital role for these proteins in response to retinoic acid (RA), a growth inhibitory signal in breast cancer cells, which may constitute the basis for their tumor suppressor activity. MCF-7 cells were infected with PALB2, BRCA1 and non targeting (SCR) shRNAs. After puromycin selection, cells were stimulated with 10microM Retinoic Acid (RA) for 24 hours
2013-09-30 | E-GEOD-45714 | biostudies-arrayexpress
Project description:Breast and ovarian cancer susceptibility genes, BRCA1 and PALB2 have enigmatic roles in cellular growth and mammalian development. While these genes are essential for growth during early developmental programs, inactivation later in adulthood leads to increased growth and formation of tumors, leading to their designation as tumor suppressors. We performed genome-wide analysis assessing their chromatin residence and gene expression responsiveness using high throughput sequencing in breast epithelial cells. These experiments revealed a critical role for BRCA1 and PALB2 in transcriptional responsiveness to NF-kB, a crucial mediator of growth and inflammatory response during development and cancer. Importantly, we also uncovered a vital role for these proteins in response to retinoic acid (RA), a growth inhibitory signal in breast cancer cells, which may constitute the basis for their tumor suppressor activity. MCF-7 cells were infected with PALB2, BRCA1, p65/RelA and non targeting (SCR) shRNAs. After puromycin selection, cells were stimulated with 10ng/ml TNF-alpha 1 hour
2013-09-30 | E-GEOD-45713 | biostudies-arrayexpress
Project description:The yeast Saccharomyces cerevisiae is a highly powerful model for systems genetics. While the advent of ordered deletion libraries has considerably facilitated yeast screening, it has also narrowed the diversity of screenable variants and precluded the exploration of the non-coding genome. Here, we present a versatile, time- and work-efficient method to functionally explore the yeast genome at an unprecedented throughput and resolution, using saturated transposon mutagenesis coupled to high-throughput sequencing. SAturated Transposon Analysis in Yeast (SATAY) allows the one-step mapping of all genetic loci in which a transposon can be inserted without disrupting a function necessary for cell growth. SATAY is especially suited to discover loci important for growth in various conditions. Here, we demonstrate that SATAY can be used to (2) reveal genetic interactions in single and multiple mutant strains, (1) reveal drug-resistant and -sensitive mutants, (3) detect not only essential genes, but also essential functional protein domains, and (4) generate not only null alleles, but also other informative genetic variants. Thus SATAY allows to easily explore the yeast genome at an unprecedented resolution and throughput.
2017-05-11 | E-MTAB-4885 | biostudies-arrayexpress
Project description:Breast and ovarian cancer susceptibility genes, BRCA1 and PALB2 have enigmatic roles in cellular growth and mammalian development. While these genes are essential for growth during early developmental programs, inactivation later in adulthood leads to increased growth and formation of tumors, leading to their designation as tumor suppressors. We performed genome-wide analysis assessing their chromatin residence and gene expression responsiveness using high throughput sequencing in breast epithelial cells. These experiments revealed a critical role for BRCA1 and PALB2 in transcriptional responsiveness to NF-kB, a crucial mediator of growth and inflammatory response during development and cancer. Importantly, we also uncovered a vital role for these proteins in response to retinoic acid (RA), a growth inhibitory signal in breast cancer cells, which may constitute the basis for their tumor suppressor activity.
2013-09-30 | GSE45714 | GEO
Project description:Breast and ovarian cancer susceptibility genes, BRCA1 and PALB2 have enigmatic roles in cellular growth and mammalian development. While these genes are essential for growth during early developmental programs, inactivation later in adulthood leads to increased growth and formation of tumors, leading to their designation as tumor suppressors. We performed genome-wide analysis assessing their chromatin residence and gene expression responsiveness using high throughput sequencing in breast epithelial cells. These experiments revealed a critical role for BRCA1 and PALB2 in transcriptional responsiveness to NF-kB, a crucial mediator of growth and inflammatory response during development and cancer. Importantly, we also uncovered a vital role for these proteins in response to retinoic acid (RA), a growth inhibitory signal in breast cancer cells, which may constitute the basis for their tumor suppressor activity.
2013-09-30 | GSE45713 | GEO
Project description:Breast and ovarian cancer susceptibility genes, BRCA1 and PALB2 have enigmatic roles in cellular growth and mammalian development. While these genes are essential for growth during early developmental programs, inactivation later in adulthood leads to increased growth and formation of tumors, leading to their designation as tumor suppressors. We performed genome-wide analysis assessing their chromatin residence and gene expression responsiveness using high throughput sequencing in breast epithelial cells. These experiments revealed a critical role for BRCA1 and PALB2 in transcriptional responsiveness to NF-kB, a crucial mediator of growth and inflammatory response during development and cancer. Importantly, we also uncovered a vital role for these proteins in response to retinoic acid (RA), a growth inhibitory signal in breast cancer cells, which may constitute the basis for their tumor suppressor activity.
2013-09-30 | GSE40591 | GEO