Browsing by author "Downs, Jessica"
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Aneuploidy tolerance caused by BRG1 loss allows chromosome gains and recovery of fitness.
Schiavoni, F; Zuazua-Villar, P; Roumeliotis, TI; Benstead-Hume, G; Pardo, M; et al. (NATURE PORTFOLIO, 2022-04-01)Aneuploidy results in decreased cellular fitness in many species and model systems. However, aneuploidy is commonly found in cancer cells and often correlates with aggressive growth, suggesting that the impact of aneuploidy ... -
BAF180 promotes cohesion and prevents genome instability and aneuploidy.
Brownlee, PM; Chambers, AL; Cloney, R; Bianchi, A; Downs, JA (CELL PRESS, 2014-03-27)BAF180, a subunit of the PBAF chromatin remodeling complex, is frequently mutated in cancer. Although PBAF regulates transcription, it remains unclear whether this is what drives tumorigenesis in cells lacking BAF180. Based ... -
CHD7 and 53BP1 regulate distinct pathways for the re-ligation of DNA double-strand breaks.
Rother, MB; Pellegrino, S; Smith, R; Gatti, M; Meisenberg, C; et al. (NATURE RESEARCH, 2020-11-13)Chromatin structure is dynamically reorganized at multiple levels in response to DNA double-strand breaks (DSBs). Yet, how the different steps of chromatin reorganization are coordinated in space and time to differentially ... -
Chromatin modifiers and remodellers in DNA repair and signalling.
Jeggo, PA; Downs, JA; Gasser, SM (ROYAL SOC, 2017-10-05) -
Defining Signatures of Arm-Wise Copy Number Change and Their Associated Drivers in Kidney Cancers.
Benstead-Hume, G; Wooller, SK; Downs, JA; Pearl, FMG (MDPI, 2019-11-16)Using pan-cancer data from The Cancer Genome Atlas (TCGA), we investigated how patterns in copy number alterations in cancer cells vary both by tissue type and as a function of genetic alteration. We find that patterns in ... -
Differential and longitudinal immune gene patterns associated with reprogrammed microenvironment and viral mimicry in response to neoadjuvant radiotherapy in rectal cancer.
Wilkins, A; Fontana, E; Nyamundanda, G; Ragulan, C; Patil, Y; et al. (BMJ PUBLISHING GROUP, 2021-03-01)BACKGROUND: Rectal cancers show a highly varied response to neoadjuvant radiotherapy/chemoradiation (RT/CRT) and the impact of the tumor immune microenvironment on this response is poorly understood. Current clinical tumor ... -
Discovery and Optimization of a Selective Ligand for the Switch/Sucrose Nonfermenting-Related Bromodomains of Polybromo Protein-1 by the Use of Virtual Screening and Hydration Analysis.
Myrianthopoulos, V; Gaboriaud-Kolar, N; Tallant, C; Hall, M-L; Grigoriou, S; et al. (AMER CHEMICAL SOC, 2016-10-13)Bromodomains (BRDs) are epigenetic interaction domains currently recognized as emerging drug targets for development of anticancer or anti-inflammatory agents. In this study, development of a selective ligand of the fifth ... -
Epigenetic changes in histone acetylation underpin resistance to the topoisomerase I inhibitor irinotecan.
Meisenberg, C; Ashour, ME; El-Shafie, L; Liao, C; Hodgson, A; et al. (Oxford University Press (OUP), 2016-10-26)The topoisomerase I (TOP1) inhibitor irinotecan triggers cell death by trapping TOP1 on DNA, generating cytotoxic protein-linked DNA breaks (PDBs). Despite its wide application in a variety of solid tumors, the mechanisms ... -
Histone isoforms and the oncohistone code.
Flaus, A; Downs, JA; Owen-Hughes, T (CURRENT BIOLOGY LTD, 2020-12-04)Recent studies have highlighted the potential for missense mutations in histones to act as oncogenic drivers, leading to the term 'oncohistones'. While histone proteins are highly conserved, they are encoded by multigene ... -
PBAF loss leads to DNA damage-induced inflammatory signaling through defective G2/M checkpoint maintenance.
Feng, H; Lane, KA; Roumeliotis, TI; Jeggo, PA; Somaiah, N; et al. (COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT, 2022-07-28)The PBRM1 subunit of the PBAF (SWI/SNF) chromatin remodeling complex is mutated in ∼40% of clear cell renal cancers. PBRM1 loss has been implicated in responses to immunotherapy in renal cancer, but the mechanism is unclear. ... -
Predicting synthetic lethal interactions using conserved patterns in protein interaction networks.
Benstead-Hume, G; Chen, X; Hopkins, SR; Lane, KA; Downs, JA; et al. (PUBLIC LIBRARY SCIENCE, 2019-04-17)In response to a need for improved treatments, a number of promising novel targeted cancer therapies are being developed that exploit human synthetic lethal interactions. This is facilitating personalised medicine strategies ... -
Removal of H2A.Z by INO80 promotes homologous recombination.
Alatwi, HE; Downs, JA (WILEY, 2015-08-01)The mammalian INO80 remodelling complex facilitates homologous recombination (HR), but the mechanism by which it does this is unclear. Budding yeast INO80 can remove H2A.Z/H2B dimers from chromatin and replace them with ... -
Repression of Transcription at DNA Breaks Requires Cohesin throughout Interphase and Prevents Genome Instability.
Meisenberg, C; Pinder, SI; Hopkins, SR; Wooller, SK; Benstead-Hume, G; et al. (CELL PRESS, 2019-01-17)Cohesin subunits are frequently mutated in cancer, but how they function as tumor suppressors is unknown. Cohesin mediates sister chromatid cohesion, but this is not always perturbed in cancer cells. Here, we identify a ... -
Requirement for PBAF in transcriptional repression and repair at DNA breaks in actively transcribed regions of chromatin.
Kakarougkas, A; Ismail, A; Chambers, AL; Riballo, E; Herbert, AD; et al. (CELL PRESS, 2014-09-04)Actively transcribed regions of the genome are vulnerable to genomic instability. Recently, it was discovered that transcription is repressed in response to neighboring DNA double-strand breaks (DSBs). It is not known ... -
The role of the SWI/SNF chromatin remodelling complex in the response to DNA double strand breaks.
Harrod, A; Lane, KA; Downs, JA (ELSEVIER, 2020-09-01)Mammalian cells possess multiple closely related SWI/SNF chromatin remodelling complexes. These complexes have been implicated in the cellular response to DNA double strand breaks (DSBs). Evidence suggests that SWI/SNF ... -
TP53 modulates radiotherapy fraction size sensitivity in normal and malignant cells.
Anbalagan, S; Ström, C; Downs, JA; Jeggo, PA; McBay, D; et al. (NATURE PORTFOLIO, 2021-03-29)Recent clinical trials in breast and prostate cancer have established that fewer, larger daily doses (fractions) of radiotherapy are safe and effective, but these do not represent personalised dosing on a patient-by-patient ...