Staff Profile
Professor David Lydall
Professor of Genome Stability
- Email: [email protected]
- Telephone: +44 (0) 191 208 5318
Qualifications
BSc Environmental Sciences University of Warwick 1984
PhD University of London 1988
Memberships
Genetics Society
Honours and Awards
Long Eaton Junior Angling Champion 1977
EMBO Long Term Fellowship 1988-1990
Research Interests
Cellular responses to damaged telomeres in budding yeast
Eukaryotic cells use a variety of mechanisms to protect themselves from the harmful effects of DNA damage. DNA repair enzymes recognise and remove damage, checkpoint control pathways delay cell division while repair occurs, and in some cases cell death or apoptosis is activated to ensure that damaged cells are removed from organisms. Human genetic defects in DNA-damage responses lead to diseases associated with ageing and cancer. For example, Werner's syndrome, a disease associated with premature human ageing, is associated with a mutation in a gene encoding a DNA repair protein. In cancer, more than half of all human tumours contain mutations in the p53 checkpoint protein.
Our lab uses genetic, molecular and biochemical approaches to understand the interplay between DNA damage responses and telomeres in the model organism Saccharomyces cerevisiae (budding yeast). The telomere is a special DNA-protein complex at the end of eukaryotic chromosomes that caps the ends of chromosomes to stop them being recognised by DNA repair and checkpoint complexes. By conditionally inactivating telomere capping proteins in yeast we can monitor the effects of DNA repair and checkpoint genes at telomeres. This permits us to generate models for how DNA damage checkpoint pathways are stimulated by uncapped telomeres and by other types of damage. Since the biochemical mechanisms underlying DNA-damage responses are largely conserved between yeast and human cells our studies in a simple, yet powerful model system, are of direct relevance to human health.
- Rodrigues J, Lydall D. Cis and trans interactions between genes encoding PAF1 complex and ESCRT machinery components in yeast. Current Genetics 2018, 64(5), 1105-1116.
- Markiewicz-Potoczny M, Lisby M, Lydall D. A critical role for Dna2 at unwound telomeres. Genetics 2018, 209(1), 129-141.
- Holstein E-M, Lawless C, Banks P, Lydall D. Genome-wide Quantitative Fitness Analysis (QFA) of yeast cultures. In: Marco Muzi-Falconi, Grant W Brown, ed. Genome Instability: Methods and Protocols. New York: Humana Press Inc, 2018, pp.575-597.
- Torrance V, Lydall D. Overlapping open reading frames strongly reduce human and yeast STN1 gene expression and affect telomere function. PLoS Genetics 2018, 14(8), e1007523.
- Rodrigues J, Lydall D. Paf1 and Ctr9, core components of the PAF1 complex, maintain low levels of telomeric repeat containing RNA. Nucleic Acids Research 2018, 46(2), 621-634.
- Lie S, Banks P, Lawless C, Lydall D, Petersen J. The contribution of non-essential Schizosaccharomyces pombe genes to fitness in response to altered nutrient supply and target of rapamycin activity. Open Biology 2018, 8(5), 180015.
- Rodrigues J, Banks P, Lydall D. Vps74 connects the golgi apparatus and telomeres in Saccharomyces cerevisiae. G3: Genes, Genomes, Genetics 2018, 8(5), 1807-1816.
- Makrantoni V, Ciesiolka A, Lawless C, Fernius J, Marston A, Lydall D, Stark MJR. A Functional Link Between Bir1 and the Saccharomyces cerevisiae Ctf19 Kinetochore Complex Revealed Through Quantitative Fitness Analysis. G3: Genes, Genomes, Genetics 2017, 7(9), 3203-3215.
- Holstein EM, Ngo G, Lawless C, Banks P, Greetham M, Wilkinson D, Lydall D. Systematic Analysis of the DNA Damage Response Network in Telomere Defective Budding Yeast. G3: Genes, Genomes, Genetics 2017, 7(7), 2375-2389.
- Heydari JJ, Lawless C, Lydall DA, Wilkinson DJ. Bayesian hierarchical modelling for inferring genetic interactions in yeast. Journal of the Royal Statistics Society: Series C (Applied Statistics) 2016, 65(3), 367-393.
- Markiewicz-Potoczny M, Lydall D. Costs, benefits and redundant mechanisms of adaption to chronic low-dose stress in yeast. Cell Cycle 2016, 15(20), 2732-2741.
- Ikeh MA, Kastora SL, Day AM, Herrero-de-Dios CM, Tarrant E, Waldron KJ, Banks AP, Bain JM, Lydall D, Veal EA, MacCallum DM, Erwig LP, Brown AJ, Quinn J. Pho4 mediates phosphate acquisition in Candida albicans and is vital for stress resistance and metal homeostasis. Molecular Biology of the Cell 2016, 27(17), 2784-2801.
- Xue Y, Marvin ME, Ivanova IG, Lydall D, Louis EJ, Maringele L. Rif1 and Exo1 regulate the genomic instability following telomere losses. Aging Cell 2016, 15(3), 553-562.
- Dubarry M, Lawless C, Banks AP, Cockell S, Lydall D. Genetic Networks Required to Coordinate Chromosome Replication by DNA Polymerases α, δ, and ε in Saccharomyces cerevisiae. G3: Genes, Genomes, Genetics 2015, 5(10), 2187-2197.
- Narayanan S, Dubarry M, Lawless C, Banks AP, Wilkinson DJ, Whitehall SK, Lydall D. Quantitative Fitness Analysis Identifies exo1∆ and Other Suppressors or Enhancers of Telomere Defects in Schizosaccharomyces pombe. PloS ONE 2015, 10(7), e0132240.
- Ngo GHP, Lydall D. The 9-1-1 checkpoint clamp coordinates resection at DNA double strand breaks. Nucleic Acids Research 2015, 43(10), 5017-5032.
- Greetham M, Skordalakes E, Lydall D, Connolly BA. The Telomere Binding Protein Cdc13 and the Single-Stranded DNA Binding Protein RPA Protect Telomeric DNA from Resection by Exonucleases. Journal of Molecular Biology 2015, 427(19), 3023-3030.
- Heydari J, Lawless C, Lydall DA, Wilkinson DJ. Fast Bayesian parameter estimation for stochastic logistic growth models. Biosystems 2014, 122, 55-72.
- Holstein E-M, Clark KRM, Lydall DA. Interplay between Nonsense-Mediated mRNA Decay and DNA Damage Response Pathways Reveals that Stn1 and Ten1 Are the Key CST Telomere-Cap Components. Cell Reports 2014, 7(4), 1259-1269.
- Ngo GHP, Balakrishnan L, Dubarry M, Campbell JL, Lydall D. The 9-1-1 checkpoint clamp stimulates DNA resection by Dna2-Sgs1 and Exo1. Nucleic Acids Research 2014, 42(16), 10516-10528.
- Andrew EJ, Merchan S, Lawless C, Banks AP, Wilkinson DJ, Lydall D. Pentose Phosphate Pathway Function Affects Tolerance to the G-Quadruplex Binder TMPyP4. PLoS One 2013, 8(6), e66242.
- Dong K, Addinall S, Lydall D, Rutherford JC. The Yeast Copper Response Is Regulated by DNA Damage. Molecular and Cellular Biology 2013, 33(20), 4041-4050.
- Banks AP, Lawless C, Lydall DA. A Quantitative Fitness Analysis Workflow. Journal of Visualised Experiments 2012, 66, e4018.
- Dewar JM, Lydall D. Similarities and differences between "uncapped" telomeres and DNA double-strand breaks. Chromosoma 2012, 121(2), 117-130.
- Weile J, Pocock M, Cockell SJ, Lord P, Dewar JM, Holstein EM, Wilkinson D, Lydall D, Hallinan J, Wipat A. Customizable views on semantically integrated networks for systems biology. Bioinformatics 2011, 27(9), 1299-1306.
- Chang H, Lawless C, Addinall SG, Oexle S, Taschuk M, Wipat A, Wilkinson DJ, Lydall D. Genome-Wide Analysis to Identify Pathways Affecting Telomere-Initiated Senescence in Budding Yeast. G3: Genes, Genomes, Genetics 2011, 1(3), 197-208.
- Addinall SG, Holstein EM, Lawless C, Yu M, Chapman K, Banks AP, Ngo HP, Maringele L, Taschuk M, Young A, Ciesiolka A, Lister AL, Wipat A, Wilkinson DJ, Lydall D. Quantitative Fitness Analysis Shows That NMD Proteins and Many Other Protein Complexes Suppress or Enhance Distinct Telomere Cap Defects. PLoS Genetics 2011, 7(4), e1001362.
- Lawless C, Wilkinson DJ, Young A, Addinall SG, Lydall DA. Colonyzer: automated quantification of micro-organism growth characteristics on solid agar. BMC Bioinformatics 2010, 11(1), 287.
- Dewar JM, Lydall D. Pif1- and Exo1-dependent nucleases coordinate checkpoint activation following telomere uncapping. EMBO Journal 2010, 29(23), 4020-4034.
- Ngo HP, Lydall D. Survival and Growth of Yeast without Telomere Capping by Cdc13 in the Absence of Sgs1, Exo1, and Rad9. PLoS Genetics 2010, 6(8), e1001072.
- Dewar JM, Lydall D. Telomere Replication: Mre11 Leads the Way. Molecular Cell 2010, 38(6), 777-779.
- Lydall D. Taming the tiger by the tail: modulation of DNA damage responses by telomeres. EMBO Journal 2009, 28(15), 2174-2187.
- LeBel C, Rosonina E, Sealey DCF, Pryde F, Lydall D, Maringele L, Harrington LA. Telomere Maintenance and Survival in Saccharomyces cerevisiae in the Absence of Telomerase and RAD52. Genetics 2009, 182(3), 671-684.
- Greenall A, Lei GY, Swan DC, James K, Wang LM, Peters H, Wipat A, Wilkinson DJ, Lydall D. A genome wide analysis of the response to uncapped telomeres in budding yeast reveals a novel role for the NAD(+) biosynthetic gene BNA2 in chromosome end protection. Genome Biology 2008, 9(10), R146.
- Addinall SG, Downey M, Yu M, Zubko MK, Dewar J, Leake A, Hallinan J, Shaw O, James K, Wilkinson DJ, Wipat A, Durocher D, Lydall DA. A Genome-wide Suppressor and Enhancer Analysis of cdc13-1 Reveals Varied Cellular Processes Influencing Telomere Capping in Saccharomyces cerevisiae. Genetics 2008, 180(4), 2251-2266.
- Morin I, Ngo H-P, Greenall A, Zubko MK, Morrice N, Lydall D. Checkpoint-dependent phosphorylation of Exo1 modulates the DNA damage response. EMBO Journal 2008, 27(18), 2400-2410.
- Lazzaro F, Sapountzi V, Granata M, Pellicioli A, Vaze M, Haber JE, Plevani P, Lydall D, Muzi-Falconi M. Histone methyltransferase Dot1 and Rad9 inhibit single-stranded DNA accumulation at DSBs and uncapped telomeres. EMBO Journal 2008, 27(10), 1502-1512.
- Proctor CJ, Lydall D, Boys RJ, Gillespie CS, Shanley D, Wilkinson DJ, Kirkwood TBL. Modelling the checkpoint response to telomere uncapping in budding yeast. Journal of the Royal Society Interface 2007, 4(12), 73-90.
- Tsolou A, Lydall D. Mrc1 protects uncapped budding yeast telomeres from exonuclease EXO1. DNA Repair 2007, 6(11), 1607-1617.
- Downey M, Houlsworth R, Maringele L, Rollie A, Brehme M, Galicia S, Guillard S, Partington M, Zubko MK, Krogan NJ, Emili A, Greenblatt JF, Harrington L, Lydall D, Durocher D. A Genome-Wide Screen Identifies the Evolutionarily Conserved KEOPS Complex as a Telomere Regulator. Cell 2006, 124(6), 1155-1168.
- Zubko MK, Maringele L, Foster SS, Lydall D. Detecting repair intermediates in vivo: Effects of DNA damage response genes on single-stranded DNA accumulation at uncapped telomeres in budding yeast. Methods in Enzymology 2006, 409, 285-300.
- Zubko MK, Lydall D. Linear chromosome maintenance in the absence of essential telomere-capping proteins. Nature Cell Biology 2006, 8(7), 734-740.
- Foster SS, Zubko MK, Guillard S, Lydall D. MRX protects telomeric DNA at uncapped telomeres of budding yeast cdc13-1 mutants. DNA Repair 2006, 5(7), 840-851.
- Lydall DA, Whitehall SK. Chromatin and the DNA damage response. DNA Repair 2005, 4(10), 1195-1207.
- Maringele L, Lydall D. Pulsed Field Gel Electrophoresis of Budding Yeast Chromosomes. In: Xiao, W, ed. Yeast Protocols. Totawa, New Jersey: Humana Press, 2005, pp.65-74.
- Maringele L, Lydall D. The PAL-mechanism of Chromosome Maintenance: Causes and Consequences. Cell Cycle 2005, 4(6), 747-751.
- Blankley RT, Lydall D. A domain of Rad9 specifically required for activation of Chk1 in budding yeast. Journal of Cell Science 2004, 117(4), 601-608.
- Zubko MK, Guillard S, Lydall D. Exo1 and Rad24 differentially regulate generation of ssDNA at telomeres of Saccharomyces cerevisiae cdc13-1 mutants. Genetics 2004, 168(1), 103-115.
- Maringele L, Lydall D. EXO1 Plays a Role in Generating Type I and Type II Survivors in Budding Yeast. Genetics 2004, 166(4), 1641-1649.
- Jia X, Weinert T, Lydall D. Mec1 and Rad53 Inhibit Formation of Single-Stranded DNA at Telomeres of Saccharomyces cerevisiae cdc13-1 Mutants. Genetics 2004, 166(2), 753-764.
- Maringele L, Lydall D. Telomerase- and recombination-independent immortalization of budding yeast. Genes and Development 2004, 18(21), 2663-2675.
- Lydall D. Hiding at the ends of yeast chromosomes: telomeres, nucleases and checkpoint pathways. Journal of Cell Science 2003, 116(20), 4057-4065.
- Maringele L, Lydall D. EXO1-dependent single-stranded DNA at telomeres activates subsets of DNA damage and spindle checkpoint pathways in budding yeast yku70Δ mutants. Genes & Development 2002, 16(15), 1919-1933.
- Booth C, Griffith E, Brady G, Lydall D. Quantitative amplification of single-stranded DNA (QAOS) demonstrates that cdc13-1 mutants generate ssDNA in a telomere to centromere direction. Nucleic Acids Research 2001, 29(21), 4414-4422.
- Lydall D. Checkpoint proteins and the metabolism of DNA damage. In: W.L. Fangman;T. Kishimoto;M. Kohiyama;C. Coath, ed. Cell Division and the Replicon: From workshop IX, The Human Frontiers Science Program based on a meeting held in Strasbourg from May 31 to June 2 1999. Strasbourg, France: Human Frontier Science Program, 2000.
- Loy CJ, Lydall D, Surana U. NDD1, a high-dosage suppressor of cdc28-1N, is essential for expression of a subset of late-S-phase-specific genes in Saccharomyces cerevisiae. Journal of Molecular Cell Biology 1999, 19(5), 3312-3327.
- Weinert T, Lydall D. Puzzles and pathways in DNA damage checkpoints in yeast. In: J.A. Nickoloff;M. Hoekstra, ed. DNA damage and repair ; Volume 1: DNA repair in prokaryotes and Lower Eukaryotes. Totawa New Jersey, USA: Humana Press, 1998.
- Lydall D, Weinert T. G2/M checkpoint genes of Saccharomyces cerevisiae: further evidence for roles in DNA replication and/or repair. Molecular and General Genetics 1997, 256(6), 638-51.
- Lydall D, Weinert T. Use of cdc13-1-induced DNA damage to study effects of checkpoint genes on DNA damage processing. Methods in Enzymology 1997, 283, 410-24.
- Lydall D, Nikolsky Y, Bishop DK, Weinert T. A meiotic recombination checkpoint controlled by mitotic checkpoint genes. Nature 1996, 383(6603), 840-3.
- Lydall D, Weinert T. From DNA damage to cell cycle arrest and suicide: a budding yeast perspective. Current Opinion in Genetics and Development 1996, 6(1), 4-11.
- Lydall D, Weinert T. Yeast checkpoint genes in DNA damage processing: implications for repair and arrest. Science 1995, 270(5241), 1488-91.
- Weinert T, Lydall D. Cell cycle checkpoints, genetic instability and cancer. Seminars in Cancer Biology 1993, 4(2), 129-40.
- Lydall D, Ammerer G, Nasmyth K. A new role for MCM1 in yeast: cell cycle regulation of SW15 transcription. Genes and Development 1991, 5(12B), 2405-19.
- Taba MR, Muroff I, Lydall D, Tebb G, Nasmyth K. Changes in a SWI4,6-DNA-binding complex occur at the time of HO gene activation in yeast. Genes and Development 1991, 5(11), 2000-13.
- Knox RJ, Lydall DA, Friedlos F, Basham C, Rawlings CJ, Roberts JJ. The Walker 256 carcinoma: a cell type inherently sensitive only to those difunctional agents that can form DNA interstrand crosslinks. Mutation Research 1991, 255(3), 227-40.
- Nasmyth K, Adolf G, Lydall D, Seddon A. The identification of a second cell cycle control on the HO promoter in yeast: cell cycle regulation of SW15 nuclear entry. Cell 1990, 62(4), 631-47.
- Knox RJ, Lydall DA, Friedlos F, Basham C, Roberts JJ. The effect of monofunctional or difunctional platinum adducts and of various other associated DNA damage on the expression of transfected DNA in mammalian cell lines sensitive or resistant to difunctional agents. Biochimica et Biophysica Acta 1987, 908(3), 214-23.
- Roberts JJ, Pera MF, Knox RJ, Friedlos F, Lydall DA. The role of platinum drug-DNA interactions in cellular toxicity and antitumour effects. In: M. Nicolini, ed. Fifth International Symposium on Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy. Boston, USA. Abano, Padua, Italy: Martinus Nijhoff Publishing, 1987, pp.16-31.
- Roberts JJ, Knox RJ, Friedlos F, Lydall DA. DNA as the target for the cytotoxic and antitumour action of platinum co-ordination complexes: comparative in vitro and in vivo studies of cisplatin and carboplatin. In: D. C. H. McBrien;T. F. Slater, ed. Biochemical Mechanisms of Platinum Antitumour Drugs. Oxford, England: IRL Press, 1986, pp.29-64.
- Knox RJ, Friedlos F, Lydall DA, Roberts JJ. Mechanism of cytotoxicity of anticancer platinum drugs: evidence that cis-diamminedichloroplatinum(II) and cis-diammine-(1,1-cyclobutanedicarboxylato)platinum(II) differ only in the kinetics of their interaction with DNA. Cancer Research 1986, 46(4 Pt 2), 1972-9.