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Kyle Miller

Miller, Kyle
Assistant Professor of Molecular Genetics and Microbiology

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Main Office: NMS 4.306 Phone: (512) 471-5045

Alternate Office: NMS 4.262 Phone: (512) 471-5266

Mailing Address:
THE UNIVERSITY OF TEXAS AT AUSTIN
Section of Molecular Genetics and Microbiology
2506 Speedway Stop A5000
Austin,TX 78712-1191


Research Summary:
DNA damage represents a formidable challenge to genome maintenance. To protect our genetic material, our cells have evolved multifaceted systems, collectively termed the DNA damage response (DDR), to detect and repair damaged DNA. It is clear that the true in vivo substrate of the DDR is not "naked" DNA but rather DNA assembled into chromatin. The structure and function of chromatin are regulated by histone modifications and chromatin modifying enzymes, which can markedly influence the DDR. Therefore, determining the interplay between the DDR and chromatin is fundamental for elucidating how cells maintain both epigenetic and genome integrity. The relevance of this research is highlighted by recent studies showing that mutations in many genes involved in the DDR and chromatin lead to cancer predisposition in humans. Therefore, we believe that deciphering the function of these pathways, both in normal and cancer cells, will contribute to the development of novel cancer therapies. Our research utilizes genetics, genomics, cell biology and molecular biology in both mouse and human tissue culture systems to gain insights into these areas of research. The lab also has interests in understanding anti-cancer drug mechanisms that function through DNA damage and chromatin. Many current drugs used in the clinic for cancer treatments act through DNA damage induction and pathways that regulate chromatin represent new targets for drug discovery. To explore this area of research, we employ a combination of chemical and molecular biology techniques to determine the in vivo interactions of small molecules (drugs) both at the cellular and molecular level. Taken together, the lab aims to engage in an active research program that applies a multifaceted and diverse approach to these questions in hopes of defining the relationship between chromatin and the DDR, as well as gaining insights into the mechanisms of cancer therapeutic drugs that act at the chromatin and DNA level.



Publications:
2012 Miller KM* and Jackson SP*, Histone marks: repairing DNA breaks within the context of chromatin, Biochemical Society Review 40(2): 370-6
2012 Rodriguez R*, Miller KM*, Forment JV, Bradshaw CR, Nikan M, Xhemalce B, Balasubramanian S1 and Jackson SP1, Small molecule inducer of double strand breaks identifies druggable alternatively-structured DNA sites. , Nature Chemical Biology 8: 301-310
2011 Miller KM and Rodriguez R, G-quadruplexes: selective DNA targeting for cancer therapeutics?, Expt. Rev. Clin. Pharmacol Vol. 4, No. 2: 139-142
2010 Miller KM, Advancements in understanding genome maintenance , Genome Biology 11: 301
2010 Devanshi J, Hebden AK, Nakamura TM, Miller KM and Cooper JP, HAATI survivors replace canonical telomeres with blocks of generic heterochromatin, Nature 467(7312): 223-7
2010 Miller KM, Tjeertes JV, Coates J, Legube G, Polo SE, Britton S and Jackson SP, Human HDAC1 and HDAC2 function in the DNA-damage response to promote DNA non-homologous end-joining, Nature Structural & Molecular Biology . Aug 29th; 17: 1144
2009 Rog O, Miller KM, Ferreira MG, and Cooper JP, Sumoylation of RecQ helicase controls the fate of dysfunctional telomeres , Mol Cell Mar 13;33(5): 559-669
2009 Tjeertes JV*, Miller KM*1 and Jackson SP1, Screen for DNA-damage-responsive histone modifications identifies H3K9Ac and H3K56Ac in human cells , EMBO J 28(13): 1878-89
2009 Germe T, Miller KM and Cooper JP, A non-canonical function of topoisomerase II in disentangling dysfunctional telomeres., EMBO J Jul 8; 28 (13): 2803-11
2009 Galanty Y, Belotserkovskaya R, Coates J, Polo SE, Miller KM and Jackson SP, SUMO E3-ligases PIAS1 and PIAS4 promote responses to DNA double-strand breaks in mammalian cells, Nature Dec 17;462 (7275): 857-8
2007 Collins SR, Miller KM, Maas NL, Roguev A, Fillingham J, Chu CS, Schuldiner M, Gebbia M, Recht J, Shales M, Ding H, Xu H, Han J, Ingvarsdottir K, Cheng B, Andrews B, Boone C, Berger SL, Hieter P, Zhang Z, Brown GW, Ingles CJ, Emili A, Allis CD, Toczyski DP, Weissman JS, Greenblatt JF and Krogan NJ, . Functional dissection of protein complexes involved in yeast chromosome biology using a genetic interaction map , Nature . Apr 12; 446 (7137): 806-10
2007 Xhemalce B, Miller KM, Driscoll R, Masumoto H, Jackson SP, Kouzarides T, Verreault A and Arcangioli B, Regulation of Histone H3 lysine 56 acetylation in Schizosaccharomyces pombe, J Biol Chem May 18;282(20): 15040-7
2006 Miller KM*, Rog O* and Cooper JP, The telomere protein Taz1 is required for conventional DNA replication through telomeres , Nature Apr 6;440 (7085): 824-8
2006 Maas NL*, Miller KM *, DeFazio LG and Toczyski DP, Cell cycle and checkpoint regulation of histone H3 K56 acetylation by Hst3/4, Mol Cell Jul 7;23 (1): 109-19
2006 Miller KM, Maas NL and Tocyzski DP , Taking It Off: Regulation of H3K56 Acetylation by Hst3 and Hst4., Cell Cycle Nov 15;5(22):
2005 Miller KM, Ferreira MG and Cooper JP, Taz1, Rap1 and Rif1 act both inter-dependently and independently to maintain telomeres, EMBO J Sep 7;24(17): 3128-35
2004 Ferreira MG*, Miller KM* and Cooper JP, . Indecent exposure. When telomeres become uncapped, Mol Cell Vol. 13 (1): 7-18
2003 Miller KM and Cooper JP, The Telomere Protein Taz1 is Required to Prevent and Repair Genomic DNA Breaks, Mol Cell Vol. 11: 303-313
2003 Beernink HTH, Miller KM, Desphande A, Bucher P and Cooper JP, Telomere Maintenance in Fission Yeast Requires an Est1 Ortholog, Current Biology Vol. 13 April 1 : 575-580
2001 Hamilton E, Miller KM, Helm KM, Langdon WY and Anderson SM, Suppression of Apoptosis Induced by Growth Factor Withdrawal by an Oncogenic Form of c-Cbl, J Biol Chem Vol. 276, 12 : 9028-9037