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,
Vol.73
(2),
pp. 212-223.e7.
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,
Vol.372
(1731),
pp. 20160279-20160279.
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,
Vol.46,
pp. 47-54.
Myrianthopoulos, V.
Gaboriaud-Kolar, N.
Tallant, C.
Hall, M.-.
Grigoriou, S.
Brownlee, P.M.
Fedorov, O.
Rogers, C.
Heidenreich, D.
Wanior, M.
Drosos, N.
Mexia, N.
Savitsky, P.
Bagratuni, T.
Kastritis, E.
Terpos, E.
Filippakopoulos, P.
Müller, S.
Skaltsounis, A.-.
Downs, J.A.
Knapp, S.
Mikros, E.
(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,
Vol.59
(19),
pp. 8787-8803.
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,
Vol.2
(1),
pp. e970072-e970072.
Alatwi, H.E.
Downs, J.A.
(2015). Removal of H2A Z by
INO
80 promotes homologous recombination. Embo reports,
Vol.16
(8),
pp. 986-994.
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,
Vol.32,
pp. 127-133.
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,
Vol.779,
pp. 16-23.
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,
Vol.112
(33),
pp. E4565-E4570.
show abstract
Faithful genome duplication and inheritance require the complete resolution of all intertwines within the parental DNA duplex. This is achieved by topoisomerase action ahead of the replication fork or by fork rotation and subsequent resolution of the DNA precatenation formed. Although fork rotation predominates at replication termination, in vitro studies have suggested that it also occurs frequently during elongation. However, the factors that influence fork rotation and how rotation and precatenation may influence other replication-associated processes are unknown. Here we analyze the causes and consequences of fork rotation in budding yeast. We find that fork rotation and precatenation preferentially occur in contexts that inhibit topoisomerase action ahead of the fork, including stable protein–DNA fragile sites and termination. However, generally, fork rotation and precatenation are actively inhibited by Timeless/Tof1 and Tipin/Csm3. In the absence of Tof1/Timeless, excessive fork rotation and precatenation cause extensive DNA damage following DNA replication. With Tof1, damage related to precatenation is focused on the fragile protein–DNA sites where fork rotation is induced. We conclude that although fork rotation and precatenation facilitate unwinding in hard-to-replicate contexts, they intrinsically disrupt normal chromosome duplication and are therefore restricted by Timeless/Tipin..
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,
Vol.6
(6),
pp. 973-981.
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,
Vol.22
(6),
pp. 805-818.
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,
Vol.55
(5),
pp. 723-732.
Jeggo, P.A.
Downs, J.A.
(2014). Roles of chromatin remodellers in DNA double strand break repair. Experimental cell research,
Vol.329
(1),
pp. 69-77.
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,
Vol.289
(33),
pp. 22614-22629.
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,
Vol.41
(19),
pp. 9168-9182.
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,
Vol.40
(15),
pp. 7393-7403.
Brownlee, P.M.
Chambers, A.L.
Oliver, A.W.
Downs, J.A.
(2012). Cancer and the bromodomains of BAF180. Biochemical society transactions,
Vol.40
(2),
pp. 364-369.
show abstract
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.
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,
Vol.26
(23),
pp. 2590-2603.
Chambers, A.L.
Downs, J.A.
(2012). The RSC and INO80 Chromatin-Remodeling Complexes in DNA Double-Strand Break Repair. ,
,
pp. 229-261.
Foster, E.R.
Downs, J.A.
(2009). Methylation of H3 K4 and K79 is not strictly dependent on H2B K123 ubiquitylation. Journal of cell biology,
Vol.184
(5),
pp. 631-638.
show abstract
Covalent modifications of histone proteins have profound consequences on chromatin structure and function. Specific modification patterns constitute a code read by effector proteins. Studies from yeast found that H3 trimethylation at K4 and K79 is dependent on ubiquitylation of H2B K123, which is termed a “trans-tail pathway.” In this study, we show that a strain unable to be ubiquitylated on H2B (K123R) is still proficient for H3 trimethylation at both K4 and K79, indicating that H3 methylation status is not solely dependent on H2B ubiquitylation. However, additional mutations in H2B result in loss of H3 methylation when combined with htb1-K123R. Consistent with this, we find that the original strain used to identify the trans-tail pathway has a genomic mutation that, when combined with H2B K123R, results in defective H3 methylation. Finally, we show that strains lacking the ubiquitin ligase Bre1 are defective for H3 methylation, suggesting that there is an additional Bre1 substrate that in combination with H2B K123 facilitates H3 methylation..
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,
Vol.5
(12),
pp. 1913-1913.
Downs, J.A.
(2008). Histone H3 K56 acetylation, chromatin assembly, and the DNA damage checkpoint. Dna repair,
Vol.7
(12),
pp. 2020-2024.
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,
Vol.35
(6),
pp. 1519-1524.
show abstract
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,
Vol.447
(7147),
pp. 951-958.
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,
Vol.6
(10),
pp. 1471-1484.
Downs, J.A.
(2007). Chromatin structure and DNA double-strand break responses in cancer progression and therapy. Oncogene,
Vol.26
(56),
pp. 7765-7772.
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,
Vol.282
(38),
pp. 27693-27701.
Bilsland, E.
Downs, J.A.
(2005). Tails of histones in DNA double-strand break repair. Mutagenesis,
Vol.20
(3),
pp. 153-163.
Harvey, A.C.
Jackson, S.P.
Downs, J.A.
(2005). Saccharomyces cerevisiae Histone H2A Ser122 Facilitates DNA Repair. Genetics,
Vol.170
(2),
pp. 543-553.
Zaid, O.
Downs, J.A.
(2005). Histones as tumour suppressor genes. Cellular and molecular life sciences,
Vol.62
(15),
pp. 1653-1656.
WARDLEWORTH, B.N.
DOWNS, J.A.
(2005). Spotting new DNA damage-responsive chromatin-binding proteins. Biochemical journal,
Vol.388
(1).
show abstract
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,
Vol.4
(10),
pp. 1373-1376.
Downs, J.A.
Jackson, S.P.
(2004). A means to a DNA end: the many roles of Ku. Nature reviews molecular cell biology,
Vol.5
(5),
pp. 367-378.
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,
Vol.16
(6),
pp. 979-990.
Downs, J.A.
Kosmidou, E.
Morgan, A.
Jackson, S.P.
(2003). Suppression of Homologous Recombination by the Saccharomyces cerevisiae Linker Histone. Molecular cell,
Vol.11
(6),
pp. 1685-1692.
Downs, J.A.
Lowndes, N.F.
Jackson, S.P.
(2000). A role for Saccharomyces cerevisiae histone H2A in DNA repair. Nature,
Vol.408
(6815),
pp. 1001-1004.
Downs, J.A.
Jackson, S.P.
(1999). Involvement of DNA End-Binding Protein Ku in Ty Element Retrotransposition. Molecular and cellular biology,
Vol.19
(9),
pp. 6260-6268.
show abstract
ABSTRACT
Saccharomyces cerevisiae Ty 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.
Epigenetic changes in histone acetylation underpin resistance to the topoisomerase I inhibitor irinotecan. Nucleic acids research,
,
pp. gkw1026-gkw1026.
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,
Vol.15
(4),
pp. e1006888-e1006888.
Foster, E.R.
Downs, J.A.
Histone H2A phosphorylation in DNA double-strand break repair. Febs journal,
Vol.272
(13),
pp. 3231-3240.
Harvey, A.C.
Downs, J.A.
What functions do linker histones provide?. Molecular microbiology,
Vol.53
(3),
pp. 771-775.
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,
Vol.7
(2),
pp. e32016-e32016.