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2002 PROGRAM 4. 3:41 Twenty-Eighth Annual 44:41.43,
8:30 am. Registration and Continental Breakfast ample, new ribozymes have been created that catalyze many of 93: "' $5 Symposrum on f 4354 $132:
Atrium (Room 1-65), William T. Young Library the chemical transformations that are essential for life, such as 11.4.4211; 453 . 5 \igg
RNA polymerization, nucleotide synthesis, aminoacylation, and 3 1" 114 Chemlst Rkt
9:00 am. Welcome by Dr. Lee T. Todd, Jr., President, peptide bond formation. These findings provide compelling sup- ,t'v" 4:434" W IVgLii
University of Kentucky - Auditorium (Room 1- portfor the "RNA world" theory, which holds that life passed through W2 "43221;." 4""??? W
62), William T. Young Library an evolutionary stage wherein all metabolic functions were guided wai- ', "45 & _:' :333.7,3{
by RNA enzymes. If true, then we can expect that an incredible 54-43:...532441; dzfi
9:05 am. introductory Remarks - Dr. Stephen M. Testa, array of RNA enzymes have been lost during the unforgiving pro- 0.114314 M I I $41: 1
University of Kentucky cess of evolution. Our laboratory has embarked on broad-based 144, - Q; 0 ecu C" i 55.ng $114.
program to study the functional properties of nucleic acids. We izgitg 34" _ 2i;.}i;1
9:10 am. Dr. Alan M. Lambowitz, University of Texas at have recently identified a new class of "self-cleaving" ribozymes i :14" '34.. ,; 3.4.2, Blolo 4%,{4
Austin (the x motif") that has a catalytic potential for RNA destruction iii gy . "" 4,3,,32,
Group II lntron Mobility by Reverse Splicing that is predicted to equal the power of natural protein enzymes. 3.2; g ,, 1, 2:3 213,13?
into DNA and its Potential Applications in We have used similar ribozymes to create a prototype "RNA biochip" '53} 3?, '31,} _T g k
Targeted Gene Disruption and DNA Insertion" that can be used as a universal biosensor platform for the rapid iii-g.- 414i 2,  ""1111
. , _ examination of genomic, proteomics and metabolomics param 29:31 2,'4":'.;..y.3;4 2.41.: "3:
Group " Introns are both catalytic RNAS ("ribozymes") and eters. Finally, our laboratory has created new enzymes that are 1. 11$ gift-34: 4
mobile genetic elements. Mobility occurs by a novel and highly made of DNA, including a series of deoxyribozyme that catalyze gmeq ggei
efficient mechanism in WhiCh the intron RNA uses its ribozyme the reactions of DNA cloning. The most significant advances made ftg $223233:
activity to insert directly into one strand Of a double-stranded DNA by our laboratory in these areas will be summarized in an effort to 15$ 1: 53: {.:. '
target site by reverse splicing. The inserted intron RNA is then address the depth of this untapped potential for nucleic acid func- "Sf-:54. 1:; . 45125144
reverse transcribed by an intronencoded reverse transcriptase, tion. Egg-"51 *9 ago
and the resulting cDNA is integrated into genomic DNA by cellular sifizgf'. 44?? , $11":ij I ":u
recombination or repair mechanisms. Because the DNA target 3110 NFL Break ywigq 1 %,,1;  1
site is reco nized in part by base pairing of the intron RNA, it is :11.-,4".".~'.1~:?-1 ' ' 32."='1""
possible togretarget group II introns to insert efficiently into virtu- 313 P-m- Dr. Stephen J- Lippard, Massachusetts Institute in 933131.); eStabIIShed m the memory 0f {3111} ' . :
ally any desired target DNA. The retargeted group ll introns can Of Technology 3. $4 4}" :53. Anna 8- Na 5,114.;- 231$;
be used for highly efficient chromosomal gene disruption in E. coli Cisplatin: From DNA Damage to Curing Cancer " 2;.3 if :1
and other bacteria at frequencies ranging from 0-1'45% WithOUt cis-DiamminedichloroplatinumdI) or Cisplatin is in widespread 15'}.- 4 2 "i 44%, ___ 1 624-1:ny
selection. in addition, the introns can be used 3 introduce tar- use for the treatment of genitourinary: head and neck, and a vari- lggg: . . Si, 7143111 f
geted chromosomal breaks, Wh'Ch can be repaired by .transfor- ety of other cancers. Cisplatin is activated in cells by aquation to 4,2913? N UCIGIC ACIdS iii4  "44 131"."
matron With an homologous DNA fragment, enabling the introduc- form cationic species that bind to DNA. The major adducts are ""2 1" 3511 , 1' $1331., 4:711; 12,.
tion 0f pim mUtations- We are attempting to deVEIOP similar ap- 1,2-intrastrand cross-links, also formed by carboplatin, which has 33 f" . 1,13. __ iiug e
preaches for targeted gene disruption and site-specific DNA in- fewer dose-limiting side effects. The structural distortion in DNA Z 8 35..." 5 ,itlif-i; "if";
sertion ' eukaryotic organisms. that accompanies platination affects replication and transcription. *5; x I: 6%}52; gig SPEAKERS 1,, 13453321;
_ . . _ . Details ofthe structure have been revealed by X-ray crystallographic "* o o _ 5'; "if .i {3, 31 24.44:;
10-30 am. Emagesswny Room 137, ChemIStW PhySICS investigations. HMG-domain and TATA-binding proteins bind with g 3 8 g, :,4
specificity to the major Cisplatin-DNA adducts, forming a stable 4: 5 <3- 1W5 Ronald R Breaker Wgg: ,3:
11:50 pm. Buffet Lunch, Faculty Club [Please return regis- platinum-DNA-protein ternary complex. The structure 0 .ne.SUCh 3). M {>4 7:73;}? 2: I - @221,
tration card b . . complex has also been determined crystallographically. Binding of o a... .- r 113-41 Alan M. Lambowrtz ave-4"? 3}" -
y April 17, 2002 for reservations. HMG- d . . . . . . M 5,; 4-,: 4:.- if _ are ,
omain proteins to the major Cisplatin-DNA adducts shields E: O .. 2, , 1%,,- , 53% Stephen J LIppard i 41,324,, 35'
2:00 pm. Dr. Ronald R. Breaker, Yale University them from nucleotide excision repair. The adducts block RNA poly- D .4? 8 '2 I 3%;
Exploring Ancient and Modern Biochemistry rrgerase, stimulating ubiqurtination of the large subunit. HMG1 Iev- g a 45.0 1%,? :5, g. 41':
using RNA Engineering es In human cancer cells bearing the estrogen or progesterone N a) a 2:1,,25 .2, .. g . . 253i???" .3;
receptor (ER or PR) are elevated followrng hormone treatment, Q, .> g Ks-s1 Q; FI'IdCiY, Apr 26, 2002 ,- ,5, 44 132.;
Recentfindings indicate that RNA and DNA haveafar greater increasing sensitivity towards Cisplatin. These findings form the 0 a a) 1? I 1 13 w
potential for catalytic function than what is manifest in extant or- basis for a clinical trial that is currently in progress. Q D 1-1 95:33 a 11 : -;{;g141 Q;
anisms. Numerous new riboz mes have been created usin a . . . - 53313' - 313 . 4 :1 44-
gombinatorial selection strategyytermed "in vitro evolution". Tgiliis 440 p.m. Meet With Speakers, Auditorium (Room 1'62 ,f'w, Department Of Chem'Stry pig's?
approach exploits the Darwinian process of molecular "survival William T' Young Library a 444 University Of Kentucky  t
ofthe-fittest" wherein new functional molecules are isolated from :.  12 ,4 - 5 ~ " 
a population of trillions of different sequence variants. For ex- (http://www.chem.uky.edu/seminars/nafflwelcome.htmI) gifg Lexmgton, KY 40506-0055 WW3 Ji
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