A5027800310- DNA Repair Mechanisms
- BRCA gene mutations in cancer
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- RNA modifications and cancer
- Nutrition, Genetics, and Disease
- Hippo pathway signaling and YAP/TAZ
- Acute Myeloid Leukemia Research
- PARP inhibition in cancer therapy
- Microtubule and mitosis dynamics
- Telomeres, Telomerase, and Senescence
- Cellular Mechanics and Interactions
- Genetically Modified Organisms Research
- RNA and protein synthesis mechanisms
- Nuclear Structure and Function
Dana-Farber Cancer Institute
2020-2021
Brigham and Women's Hospital
2020
Harvard University
2020
Queen's University Belfast
2014-2019
Sidney Kimmel Comprehensive Cancer Center
2014
Johns Hopkins University
2014
University of Naples Federico II
2014
Queensland University of Technology
2014
Germline mutations in BRCA1 predispose carriers to a high incidence of breast and ovarian cancers. functions maintain genomic stability through critical roles DNA repair, cell-cycle arrest, transcriptional control. A major question has been why loss or mutation leads tumors mainly estrogen-regulated tissues, given that essential all cell types. Here, we report estrogen metabolites can cause double-strand breaks (DSB) receptor-α-negative cells is required repair these DSBs prevent...
mRNA splicing and export plays a key role in the regulation of gene expression, with recent evidence suggesting an additional layer expression cellular function through selective genes within specific pathways. Here we describe for RNA processing factors THRAP3 BCLAF1 DNA damage response (DDR) pathway, pathway involved maintenance genomic stability prevention oncogenic transformation. We show that loss and/or leads to sensitivity damaging agents, defective repair instability. Additionally,...
R-loop structures act as modulators of physiological processes such transcription termination, gene regulation, and DNA repair. However, they can cause transcription-replication conflicts give rise to genomic instability, particularly at telomeres, which are prone forming secondary structures. Here, we demonstrate that BRCA1 binds TERRA RNA, directly physically via its N-terminal nuclear localization sequence, well telomere-specific shelterin proteins in an R-loop-, a cell cycle-dependent...
Abstract Myelodysplastic syndromes (MDS) are haematopoietic malignancies that characterised by a heterogeneous clinical course. In recent years, sequencing efforts have uncovered recurrent somatic mutations within RNA splicing factors, including SF3B1, SRSF2, U2AF1 and ZRSR2 . The most frequently mutated gene is SF3B1 , in 17% of MDS patients. While their effects on been well characterised, much remains to be explored about more far-reaching cellular homeostasis. Given mRNA nuclear export...
BRCA1 promotes error-free, homologous recombination-mediated repair (HRR) of DNA double-stranded breaks (DSBs). When excessive and uncontrolled, HRR activity illegitimate recombination genome disorder. We others have observed that the BRCA1-associated protein RAP80 recruits to postdamage nuclear foci, these chromatin structures then restrict amplitude BRCA1-driven HRR. What remains unclear is how this process regulated. Here we report both poly-ADP ribosylation (PARsylation) presence...
Abstract Histological grading provides prognostic stratification of colorectal cancer (CRC) by scoring heterogeneous phenotypes. Features aggressiveness include aberrant mitotic spindle configurations, chromosomal breakage, and bizarre multicellular morphology, but pathobiology is poorly understood. Protein kinase C zeta (PKCz) controls dynamics, chromosome segregation, patterns, its role in CRC phenotype evolution remains unclear. Here, we show that PKCz couples genome segregation to...
<p>PDF file - 124K</p>
<p>PDF file - 2823K, Supplementary Figure 1. Estrogen metabolites cause DNA double strand breaks in S- phase cells. 2. BRCA1 supresses estrogen metabolite mediated DSBs and is required for their repair. 3. its induce a dose time dependent manner. 4. suppresses induced damage mutant breast cancer 5. BRCA2 are repair of MCF10A MCF7 6. BRCA1, but not BRCA2, by repressing CYP1A1 expression cells.</p>
<p>PDF file - 75K</p>
<p>PDF file - 75K</p>
<div>Abstract<p>Germline mutations in <i>BRCA1</i> predispose carriers to a high incidence of breast and ovarian cancers. BRCA1 functions maintain genomic stability through critical roles DNA repair, cell-cycle arrest, transcriptional control. A major question has been why loss or mutation leads tumors mainly estrogen-regulated tissues, given that essential all cell types. Here, we report estrogen metabolites can cause double-strand breaks (DSB) receptor-α–negative...
<div>Abstract<p>Germline mutations in <i>BRCA1</i> predispose carriers to a high incidence of breast and ovarian cancers. BRCA1 functions maintain genomic stability through critical roles DNA repair, cell-cycle arrest, transcriptional control. A major question has been why loss or mutation leads tumors mainly estrogen-regulated tissues, given that essential all cell types. Here, we report estrogen metabolites can cause double-strand breaks (DSB) receptor-α–negative...
<p>PDF file - 2823K, Supplementary Figure 1. Estrogen metabolites cause DNA double strand breaks in S- phase cells. 2. BRCA1 supresses estrogen metabolite mediated DSBs and is required for their repair. 3. its induce a dose time dependent manner. 4. suppresses induced damage mutant breast cancer 5. BRCA2 are repair of MCF10A MCF7 6. BRCA1, but not BRCA2, by repressing CYP1A1 expression cells.</p>
<p>PDF file - 124K</p>