Meisenberg, C., Pinder, S.I., Hopkins, S.R., Wooller, S.K., Benstead-Hume, G., Pearl, F.M., Jeggo, P.A. & Downs, J.A.
(2019). Repression of Transcription at DNA Breaks Requires Cohesin throughout Interphase and Prevents Genome Instability. Molecular cell,
Jeggo, P.A., Downs, J.A. & Gasser, S.M.
(2017). Chromatin modifiers and remodellers in DNA repair and signalling. Philosophical transactions of the royal society b: biological sciences,
Hopkins, S.R., McGregor, G.A., Murray, J.M., Downs, J.A. & Savic, V.
(2016). Novel synthetic lethality screening method identifies TIP60-dependent radiation sensitivity in the absence of BAF180. Dna repair,
Myrianthopoulos, V., Gaboriaud-Kolar, N., Tallant, C., Hall, M.-., Grigoriou, S., Brownlee, P.M., Fedorov, O., Rogers, C., Heidenreich, D., Wanior, M., et al.
(2016). 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. Journal of medicinal chemistry,
Kakarougkas, A., Downs, J.A. & Jeggo, P.A.
(2015). The PBAF chromatin remodeling complex represses transcription and promotes rapid repair at DNA double-strand breaks. Molecular & cellular oncology,
Brownlee, P.M., Meisenberg, C. & Downs, J.A.
(2015). The SWI/SNF chromatin remodelling complex: Its role in maintaining genome stability and preventing tumourigenesis. Dna repair,
Alatwi, H.E. & Downs, J.A.
(2015). Removal of H2A Z by
80 promotes homologous recombination. Embo reports,
Niimi, A., Hopkins, S.R., Downs, J.A. & Masutani, C.
(2015). The BAH domain of BAF180 is required for PCNA ubiquitination. Mutation research/fundamental and molecular mechanisms of mutagenesis,
Schalbetter, S.A., Mansoubi, S., Chambers, A.L., Downs, J.A. & Baxter, J.
(2015). Fork rotation and DNA precatenation are restricted during DNA replication to prevent chromosomal instability. Proceedings of the national academy of sciences,
Brownlee, P.M., Chambers, A.L., Cloney, R., Bianchi, A. & Downs, J.A.
(2014). BAF180 Promotes Cohesion and Prevents Genome Instability and Aneuploidy. Cell reports,
Pal, M., Morgan, M., Phelps, S.E., Roe, S.M., Parry-Morris, S., Downs, J.A., Polier, S., Pearl, L.H. & Prodromou, C.
(2014). Structural Basis for Phosphorylation-Dependent Recruitment of Tel2 to Hsp90 by Pih1. Structure,
Kakarougkas, A., Ismail, A., Chambers, A.L., Riballo, E., Herbert, A.D., Künzel, J., Löbrich, M., Jeggo, P.A. & Downs, J.A.
(2014). Requirement for PBAF in Transcriptional Repression and Repair at DNA Breaks in Actively Transcribed Regions of Chromatin. Molecular cell,
Jeggo, P.A. & Downs, J.A.
(2014). Roles of chromatin remodellers in DNA double strand break repair. Experimental cell research,
López-Perrote, A., Alatwi, H.E., Torreira, E., Ismail, A., Ayora, S., Downs, J.A. & Llorca, O.
(2014). Structure of Yin Yang 1 Oligomers That Cooperate with RuvBL1-RuvBL2 ATPases. Journal of biological chemistry,
Chambers, A.L., Pearl, L.H., Oliver, A.W. & Downs, J.A.
(2013). The BAH domain of Rsc2 is a histone H3 binding domain. Nucleic acids research,
Niimi, A., Chambers, A.L., Downs, J.A. & Lehmann, A.R.
(2012). A role for chromatin remodellers in replication of damaged DNA. Nucleic acids research,
Chambers, A.L., Ormerod, G., Durley, S.C., Sing, T.L., Brown, G.W., Kent, N.A. & Downs, J.A.
(2012). The INO80 chromatin remodeling complex prevents polyploidy and maintains normal chromatin structure at centromeres. Genes & development,
Brownlee, P.M., Chambers, A.L., Oliver, A.W. & Downs, J.A.
(2012). Cancer and the bromodomains of BAF180. Biochemical society transactions,
Chromatin remodelling complexes alter the structure of chromatin and have central roles in all DNA-templated activities, including regulation of gene expression and DNA repair. Mutations in subunits of the PBAF (polybromo/Brg1-associated factor) or SWI/SNF-B remodelling complex, including BAF180, are frequently associated with cancer. There are six potential acetyl-lysine-binding BDs (bromodomains) in BAF180, which may function to target the PBAF complex to promoters or sites of DNA repair. In the present review, we discuss what is currently known about the BDs of BAF180 and their potential significance in cancer..
Chambers, A.L. & Downs, J.A.
(2012). The RSC and INO80 Chromatin-Remodeling Complexes in DNA Double-Strand Break Repair. ,
Foster, E.R. & Downs, J.A.
(2009). Methylation of H3 K4 and K79 is not strictly dependent on H2B K123 ubiquitylation. The journal of cell biology,
Titman, C.M., Downs, J.A., Oliver, S.G., Carmichael, P.L., Scott, A.D. & Griffin, J.L.
(2009). A metabolomic and multivariate statistical process to assess the effects of genotoxins in Saccharomycescerevisiae. Molecular biosystems,
(2008). Histone H3 K56 acetylation, chromatin assembly, and the DNA damage checkpoint. Dna repair,
Chambers, A.L. & Downs, J.A.
(2007). The contribution of the budding yeast histone H2A C-terminal tail to DNA-damage responses. Biochemical society transactions,
The cellular response to DNA damage involves extensive interaction with and manipulation of chromatin. This includes the detection and repair of the DNA lesion, but there are also transcriptional responses to DNA damage, involving the up- or down-regulation of numerous genes. Therefore changes to chromatin structure, including covalent modification of histone proteins, are known to occur during DNA-damage responses. One of the most well characterized DNA-damage-responsive chromatin modification events is the phosphorylation of the SQ motif found in the C-terminal tail of histone H2A or the H2AX variant in higher eukaryotes. In the budding yeast, a number of additional residues in this region of histone H2A that contribute to the cellular response to DNA damage have been identified, providing an insight into the nature and complexity of the DNA-damage histone code..
Downs, J.A., Nussenzweig, M.C. & Nussenzweig, A.
(2007). Chromatin dynamics and the preservation of genetic information. Nature,
Bilsland, E., Hult, M., Bell, S.D., Sunnerhagen, P. & Downs, J.A.
(2007). The Bre5/Ubp3 ubiquitin protease complex from budding yeast contributes to the cellular response to DNA damage. Dna repair,
(2007). Chromatin structure and DNA double-strand break responses in cancer progression and therapy. Oncogene,
Kent, N.A., Chambers, A.L. & Downs, J.A.
(2007). Dual Chromatin Remodeling Roles for RSC during DNA Double Strand Break Induction and Repair at the YeastMATLocus. Journal of biological chemistry,
Bilsland, E. & Downs, J.A.
(2005). Tails of histones in DNA double-strand break repair. Mutagenesis,
Harvey, A.C., Jackson, S.P. & Downs, J.A.
(2005). Saccharomyces cerevisiae Histone H2A Ser122 Facilitates DNA Repair. Genetics,
Zaid, O. & Downs, J.A.
(2005). Histones as tumour suppressor genes. Cellular and molecular life sciences,
WARDLEWORTH, B.N. & DOWNS, J.A.
(2005). Spotting new DNA damage-responsive chromatin-binding proteins. Biochemical journal,
In response to DNA damage, cells initiate multiple repair mechanisms that all contribute to the survival of both the cell and the organism. These responses are numerous and variable, and can include cell cycle arrest, transcriptional activation of DNA repair genes and relocalization of repair proteins to sites of DNA damage. If all else fails, in multicellular organisms the initiation of apoptosis is also a potential cellular response to DNA damage. Despite a wealth of information about these events, it is clear that we do not yet have a comprehensive picture of the cellular responses to DNA damage. In this issue of the Biochemical Journal, a proteomics approach was used by Lee et al. to identify proteins that bind to chromatin in a DNA damage-inducible manner. The proteins identified, nucleophosmin, hnRNP C1 (heterogeneous nuclear ribonucleoprotein C1) and hnRNP C2, were proteins that would not necessarily have been predicted to behave this way. These studies have the potential to be extended and contribute to our knowledge of the cellular response to DNA damage..
Downs, J.A. & Cote, J.
(2005). Dynamics of Chromatin during the Repair of DNA Double-Strand Breaks. Cell cycle,
Downs, J.A. & Jackson, S.P.
(2004). A means to a DNA end: the many roles of Ku. Nature reviews molecular cell biology,
Downs, J.A., Allard, S., Jobin-Robitaille, O., Javaheri, A., Auger, A., Bouchard, N., Kron, S.J., Jackson, S.P. & Côté, J.
(2004). Binding of Chromatin-Modifying Activities to Phosphorylated Histone H2A at DNA Damage Sites. Molecular cell,
Downs, J.A., Kosmidou, E., Morgan, A. & Jackson, S.P.
(2003). Suppression of Homologous Recombination by the Saccharomyces cerevisiae Linker Histone. Molecular cell,
Downs, J.A., Lowndes, N.F. & Jackson, S.P.
(2000). A role for Saccharomyces cerevisiae histone H2A in DNA repair. Nature,
Downs, J.A. & Jackson, S.P.
(1999). Involvement of DNA End-Binding Protein Ku in Ty Element Retrotransposition. Molecular and cellular biology,
Saccharomyces cerevisiaeTy elements are retrotransposons whose life cycles are strikingly similar to those of retroviruses. They transpose via an RNA intermediate that is converted to linear double-stranded cDNA and then inserted into the host genome. Although Ty integration is mediated by the element-encoded integrase, it has been proposed that host factors are involved in this process. Here, we show that the DNA end-binding protein Ku, which functions in DNA double-strand break repair, potentiates retrotransposition. Specifically, by using a galactose-inducible Ty1 system, we found that in vivo, Ty1 retrotransposition rates were substantially reduced in the absence of Ku. In contrast, this phenotype was not observed with yeast strains containing mutations in other genes that are involved in DNA repair. We present evidence that Ku associates with Ty1 viruslike particles both in vitro and in vivo. These results provide an additional role for Ku and suggest that it might function in the life cycles of retroelements in other systems..
Meisenberg, C., Ashour, M.E., El-Shafie, L., Liao, C., Hodgson, A., Pilborough, A., Khurram, S.A., Downs, J.A., Ward, S.E. & El-Khamisy, S.F., et al.
Epigenetic changes in histone acetylation underpin resistance to the topoisomerase I inhibitor irinotecan. Nucleic acids research,
Chambers, A.L., Brownlee, P.M., Durley, S.C., Beacham, T., Kent, N.A. & Downs, J.A.
The Two Different Isoforms of the RSC Chromatin Remodeling Complex Play Distinct Roles in DNA Damage Responses. Plos one,
Foster, E.R. & Downs, J.A.
Histone H2A phosphorylation in DNA double-strand break repair. Febs journal,
Harvey, A.C. & Downs, J.A.
What functions do linker histones provide?. Molecular microbiology,
Benstead-Hume, G., Chen, X., Hopkins, S.R., Lane, K.A., Downs, J.A. & Pearl, F.M.
Predicting synthetic lethal interactions using conserved patterns in protein interaction networks. Plos computational biology,