A5089227056- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- PARP inhibition in cancer therapy
- Carcinogens and Genotoxicity Assessment
- Genomics and Chromatin Dynamics
- BRCA gene mutations in cancer
- Cancer, Hypoxia, and Metabolism
- Chromosomal and Genetic Variations
- Peptidase Inhibition and Analysis
- Pluripotent Stem Cells Research
- Prostate Cancer Treatment and Research
- Epigenetics and DNA Methylation
- Microtubule and mitosis dynamics
- Cancer-related Molecular Pathways
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Mitochondrial Function and Pathology
- Virus-based gene therapy research
- Glioma Diagnosis and Treatment
- RNA and protein synthesis mechanisms
- RNA Interference and Gene Delivery
- Radiopharmaceutical Chemistry and Applications
- Plant Genetic and Mutation Studies
- Semiconductor materials and devices
- Genetic factors in colorectal cancer
Kettering University
2009-2024
Memorial Sloan Kettering Cancer Center
2015-2024
Developmental Studies Center
2019
Cornell University
2003-2017
Weill Cornell Medicine
2017
Candy’s Place
2014
Albert Einstein College of Medicine
2005-2013
UNC Lineberger Comprehensive Cancer Center
2013
University of North Carolina at Chapel Hill
2013
New York Proton Center
2013
Andrew J. Pierce, Roger D. Johnson, Larry H. Thompson, and Maria Jasin Cell Biology Program, Memorial Sloan-Kettering Cancer Center Cornell University Graduate School of Medical Sciences, New York, York 10021 USA; Biotechnology Research Lawrence Livermore National Laboratory, Livermore, California 94551 USA
Germline mutations in BRCA1 confer a high risk of breast and ovarian tumors. The role tumor suppression is not yet understood, but both transcription repair functions have been ascribed. Evidence that involved DNA stems from its association with RAD51, homolog the yeast protein double-strand breaks (DSBs) by homologous recombination. We report here Brca1-deficient mouse embryonic stem cells impaired chromosomal DSBs relative frequencies nonhomologous integration DSB were also altered....
To maintain genomic integrity, double-strand breaks (DSBs) in chromosomal DNA must be repaired. In mammalian systems, the analysis of repair DSBs has been limited by inability to introduce well-defined DNA. this study, we created specific mouse chromosomes for first time, using an expression system a rare-cutting endonuclease, I-SceI. A genetic assay devised monitor DSBs, whereby cleavage sites I-SceI have integrated into genome two tandem neomycin phosphotransferase genes. We find that is...
Mammalian cells have been presumed to repair potentially lethal chromosomal double-strand breaks (DSBs) in large part by processes that do not require homology the break site. This contrasts with Saccharomyces cerevisiae where major DSB pathway is homologous recombination. Recently, it has determined DSBs genomic DNA mammalian can stimulate recombination as much 3 or 4 orders of magnitude, suggesting homology-directed may play an important role breaks. To determine whether use...
The Alternative Lengthening of Telomeres (ALT) pathway is a telomerase-independent for telomere maintenance that active in significant subset human cancers and vitro immortalized cell lines. ALT thought to involve templated extension telomeres through homologous recombination, but the genetic or epigenetic changes unleash are not known. Recently, mutations ATRX/DAXX chromatin remodeling complex histone H3.3 were found correlate with features pancreatic neuroendocrine cancers, pediatric...
Double-strand breaks introduced into DNA in vivo have been shown to enhance homologous recombination a variety of chromosomal and extrachromosomal loci Saccharomyces cerevisiae. To introduce double-strand at defined locations mammalian cells, we constructed expression vector for modified form I-Sce I, yeast mitochondrial intron-encoded endonuclease with an 18-bp recognition sequence. Expression the I COS1 cells results cleavage model substrates enhanced recombination, as assayed by...
Abstract We demonstrate that the androgen receptor (AR) regulates a transcriptional program of DNA repair genes promotes prostate cancer radioresistance, providing potential mechanism by which deprivation therapy synergizes with ionizing radiation. Using model castration-resistant cancer, we show second-generation antiandrogen results in downregulation genes. Next, primary cancers display significant spectrum AR output, correlates expression set RNA-seq and ChIP-seq, define these are both...
Repair of chromosomal breaks is essential for cellular viability, but misrepair generates mutations and gross rearrangements. We investigated the interrelationship between two homologous-repair pathways, i.e., mutagenic single-strand annealing (SSA) precise homology-directed repair (HDR). For this, we analyzed efficiency in mammalian cells which double-strand break (DSB) components were disrupted. observed an inverse relationship HDR SSA when RAD51 or BRCA2 was impaired, reduced increased....
Meiotic crossovers are produced when programmed double-strand breaks (DSBs) repaired by recombination from homologous chromosomes (homologues). In a wide variety of organisms, meiotic HORMA-domain proteins required to direct DSB repair towards homologues. This inter-homologue bias is for efficient homology search, homologue alignment, and crossover formation. also implicated in other processes related formation, including inhibition promiscuous formation the synaptonemal complex (SC),...
Fanconi anemia (FA) is a recessive disorder characterized by congenital abnormalities, progressive bone-marrow failure, and cancer susceptibility. Cells from FA patients are hypersensitive to agents that produce DNA crosslinks and, after treatment with these agents, have pronounced chromosome breakage other cytogenetic abnormalities. Eight FANC genes been cloned, the encoded proteins interact in common cellular pathway. DNA-damaging activate monoubiquitination of FANCD2, resulting its...
Abstract High-grade epithelial ovarian carcinomas containing mutated BRCA1 or BRCA2 (BRCA1/2) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and PARP inhibitors (PARPi), while restoration of HR function due secondary mutations in BRCA1/2 has been recognized as an important resistance mechanism. We sequenced core pathway 12 pairs pretreatment postprogression tumor biopsy samples collected from patients ARIEL2 Part 1, a phase II study the PARPi rucaparib...