molecular_genetics_ms1.txt

• 1. nitrogen base
• 2. sugar
• 3. phosphate

C. linear

globular

isomerases

5' --- 3'

*leading strand

• Capping provides stability to the mRNA
• * made up of guanine nucleotide with 2 phosphate

3' end

Adenine bases -- approx. 200

provides stability to the mRNA and also appears to control the movement of the mRNA across the nuclear envelope.

extrons

small nuclear ribonucleoproteins or snRNP's

A - RIGHT HANDED; ASSOCIATED WITH DNA/RNA HYBRIDS

B - RIGHT HANDED; MOST COMMON IN HUMANS.

Z - LEFT HANDED; FORMS ZIG-ZAG PATTERN.

USED DURING CELL DIVISION AS THE ATTACHMENT POINT FOR SPINDLE FIBERS

USED TO MAINTAIN CHROM INTEGRITY BY CAPPING OFF THE ENDS OF THE LINEAR CHROM

OCTAMER CONSISTING OF 2 COPIES EACH OF THE CORE HISTONES H2A, H2B, H3, H4, AND LINKER HISTONE H1.

RICH IN BASIC AMINO ACIDS (LYS, ARG) AND ARE POSITIVELY CHARGED AT PHYS PH ALLOWING THEM TO BIND TO NEGATIVE CHARGED DNA

STABLE IN PRESENCE OF DNA

COVALENT METHYLATION OF THE CYTOSINE BASES IN DNA

REVERSIBLE MODIFICAITONS OF HISTONES BY ACYLATION OF N-TERMINAL AMINO ACIDS

INVOLVED IN GENE SILENCING AND CONSIDERED EPIGENETIC

CHROM 16 CONTAIN DIFFERENT TYPES OF ALPHA HEMOGLOBIN

DEFECTIVE ALPHA GENES CAUSE THALASSEMIA RESULTING IN MILD TO SEVERE ANEMIA AND EVEN DEATH

CHROM 11, SLIGHT CHANGE CAUSES DISASTEROUS EFFECTS

SICKLE-CELL ANEMIA

SHORT REGION OF 20-50 REPEATS.

DIFFERENCES IN THESE REPEATS IS THE BASIS FOR DNA FINGERPRINTING

POLYMORPHIC WITH 1-15 REPEATS.

DI, TRI, OR VNTR (VARIABLE # TANDEM REPEATS)

HUNTINGTON'S CHORIA (TRI CAG REPEAT >30)

FOUND IN ALL EUK GENOMES

PROPAGATE BY RNA MEDIATED TRANSPOSITION

LONG INTERSPERSED NUCLEAR ELEMENTS

TRANSCRIBED INTO RNA USING RNA POL I PROMOTER LOCATED INSIDE GENE

CODE FOR ENZYME REVERSE TRANSCRIPTASE AND ENDONUCLEASE (RNase)

COPY THEMSELVES AND ENLARGE GENOME (21% IS ARE LINES)

SMALL INTERSPERSED NUCLEAR ELEMENTS

REVERSE TRANSCRIBED RNA ORIGINALLY TRANSCRIBED BY RNA POL III INTO tRNA, rRNA, and other small nuclear RNA

DO NOT CONTAIN ANY CODING SEQUENCES

31% OF GENOME

REPEATED PATERN CAN BE 1 TO SEVERAL THOUSAND BP LONG AND IN TOTAL CAN BE SEVERAL MEGA BP

MOSTLY IN TELOMERIC AND CENTROMERIC REGIONS

3'-UNTRANSLATED REGION

POLY-A SIGNAL FOR POST TRANSCRIPTIONAL MODIFICATION

BINDING SITES FOR PROTEINS

BINDING SITES FOR miRNA

(1) 5'-TERMINAL PHOSPHATE GROUP

(2) ACCEPTOR STEM FOR ADDITION OF 3' CCA SEQUENCE

(3) CCA TAIL ON 3' END ADDED POST-TRANSCRIPTIONALLY. WHERE AMINO ACID ATTACHES

(4) D ARM. 4 BP LOOP OFTEN CONTAINING DIHYDRURIDINE

(5) ANTICODON ARM

(6) T ARM CONTAINING PSEUDO-URIDINE

28S, 18S, 5.8S, AND 5S + 82 PROTEINS

MAKE 80S RIBOSOMES (60S LARGE AND 40S SMALL)

60S (28S, 5.8S, 5S + 49 PROTEINS)

40S (18S + 33 PROTEINS)

80-85% OF TOTAL RNA FOUND IN AVERAGE EUK CELL

SMALL NUCLEAR RNA FOUND WITHIN NUCLEUS OF EUK CELLS

TRANSCRIBED BY RNA POL II OR III

INVOLVED IN RNA SPLICING, REGULATION OF TRANSCRIPTION FACTORS, AND MAINTAINING TELOMERES

microRNA POST-TRANSCRIPTIONAL REGULATORS THAT BIND TO COMPLEMENTARY SEQUENCES IN THE 3' UTR OF TARGET mRNA

USUALLY BLOCK TRANSLATION OR ACCELERATE DEGRADATION

CAN CAUSE METHYLATION OF GENES

TARGET ABOUT 60% OF MAMMALIAN GENES

FORMATION OF PRE-INITIATION REPLICATION COMPLEX (pre-RC = ORC + MCM) REFERED TO AS LICENSING

Cdc6 LOADS MCM COMPLEX TO ORIGIN. MADE ONLY DURING G1 PHASE, PHOSPHORYLATED AT S PHASE AND DEACTIVATED.

MCM IS A DNA HELICASE

SINGLE STRANDED BINDING PROTEINS BIND TO DNA DURING SYNTHESIS TO KEEP FROM ANNEALING AND STABILIZE DNA TO ALLOW 100X FASTER REPLICATION

DNA POL ALPHA AND DELTA

DNA POL ALPHA ADDS RNA PRIMERS

PRIMERS REMOVED BY RNAse H & FLAP ENDONULEASES (FENs)

REPLACED BY DNA POL DELTA & LINKED BY DNA LIGASE

SYNTHS AN RNA PRIMER AT INITIATION SITES FOR LEADING/LAGGING STRAND

PROVIDES 3'OH FOR ELONGATION WITH DNA NUCLEOTIDES

IMPLICATED IN DNA BASE EXCISION REPAIR

REPLICATES AND REPAIRS MITOCHONDRIAL DNA

HAS PROOFREADING 3'-5' EXONUCLEASE ACTIVITY

HIGHLY PROCESSIVE 5'-3' SYNTH

PROOFREADING 3'-5' EXONUCLEASE ACTIVITY

MAIN POL FOR DNA LEADING/LAGGING STRAND SYNTH AND GAP FILLING AFTER REMOVAL

CONTRIBUTE TO DNA SYNTH BY FORMING A SLIDING CLAMP AROUND DNA

HELPS RELEASE DNA POL

PROLIFERATING CELL NUCLEAR ANTIGENS

PROTEIN THAT ACTS AS A PROCESSIVITY FACTOR FOR DNA POL DELTA IN EUK CELLS

TYPE OF DNA CLAMP

EXTENDS REPETITIVE SEQUENCES OF THE TELOMERE TO PREVENT DEGRADATION AND CHROM FUSION

REVERSE TRANSCRIPTASE THAT CARRIES OWN RNA MOLECULE, WHICH IS USED AS TEMPLATE DURING ELONGATION

REGULATED DURING DEVELOPMENT AND HAS VERY LOW ACTIVITY IN SOMATIC CELLS (AGING, CANCER)

BIDIRECTIONAL

SINGLE ORIGIN

POL I -- DNA REPAIR, HAS 5'-3' ACTIVITY AND BOTH 3'-5' AND 5'-3' EXONUCLEASE ACTIVITY (REMOVING DNA PRIMERS) AND FILLS GAPS AFTER REMOVAL OF RNA PRIMERS

POL II -- REPAIR OF DAMAGED DNA. HAS 3'-5' EXONUCLEASE ACTIVITY

POL III -- MAIN POL IN PROC SYNTH. HAS 5'-3' SYNTH AND 3'-5' PROOFREADING

ANTIBIOTIC

TARGET DNA GYRASE (TOPO I & II) AND BLOCK SYNTH

USED TO TREAT MRSA

ANTIBIOTIC

EFFECTIVE AGAINST BOTH GRAM + & -

PREVENTS REANNEALING OF DOUBLE-SRTANDED BREAK

TREAT AGAINST URINARY TRACT INFECTIONS

ANTIBIOTIC

ACTS ON TOPOs

TREATS ANTHRAX

CAN TRANSCRIBE BOTH DNA AND RNA

RNase ACTIVITY REMOVES RNA FROM DNA/RNA HYBRIDS AND MAKES 2X STRANDED DNA

LACKS PROOFREADING & MAKES LOTS OF MISTAKES (1 IN 2,000 -- ABOUT 5X)

(GAG) GROUP SPECIFIC PROTEINS MAKES CORE AND STRUCTURAL PROTEINS (VIRAL CAPSID)

• POLIMERASE CODES FOR:
• --REVERSE TRANSCRIPTASE
• --PROTEASE CLEAVES PROTEINS TO MAKE GAG AND POL
• --INTEGRASE FOR INTEGRATION INTO HOST DNA

ENV CODES FOR ENVELOPE PROTEINS ESSENTIAL FOR VIRAL ENTRY INTO CELL

LTR LONG TERMINAL REPEATS

POL POLYMERASE GENE

ENV ENVELOPE GENE

TAT TRANSACTIVATOR PROTEIN

REV REGULATOR OF EXPRESSION

VIF VIRAL INFECTIVITY

VPU VIRAL PROTEIN U

VPR VIRAL PROTEIN R

NEF NEGATIVE-REGULATION PROTEIN

DIMER RNA

5' CAP AND 3'POLLY A TAIL

TERMINAL NONCODING REGIONS IMPORTANT FOR REPLICATION AND INTERNAL REGIONS THAT ENCODE VIRAL PROTEINS

BINDS TO TOPO I AND DNA COMPLEX

PREVENTS RELIGATION

WORKS WITH CTP

DNA POL INHIBITOR

CONVERTED TO TRI-PHOS FORM THEN ACTS AS CHAIN TERMINATOR

BLOCKS RIBONUCLEOTIDE REDICTASE IN CDP FORM

REPLACES RIBOSE SUGAR WITH ARABINOSE

CANCER DRUG

PLATINUM COMPLEXES CAUSE CROSSLINKING OF DNA AND TRIGGERS APOPTOSIS

ANTIRETROVIRAL DRUG

NUCLEOSIDE ANALOG REVERSE TRANSCRIPTASE INHIBITOR (NRTI)

RESULTS IN CHAIN TERMINATION

SHOWS SELECTIVITY FOR HIV CELLS

HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART)

HIV

(3TC) HIV

REVERSE TRANS INHIBITOR

HERPES REPLICATION BLOCKER

SUGAR RING REPLACED BY OPEN CHAIN STRUCTURE

RESULTS IN ACYLCO-GTP HAVING HIGHER AFFINITY FOR VIRAL POL, CAUSING CHAIN TERMINATION

1) REQUIRE DNA TEMPLATE

2) REQUIRE ALL 4 NUCLEOTIDE TRIPHOSPHATES AS SUBSTRATES

3) CATALYZE THE SYNTHESIS OF NEW RNA MOLECULE IN A 5' TO 3' DIRECTION

REARRANGEMENT OF CHROMATIN CONTAINING THE PROMOTER SEQUENCE

BINDING OF TRANSCRIPTION FACTORS TO PROMOTER AND ENHANCER (NOT ALL GENES CONTAIN ENHANCER)

BINDING OF RNA POL TO PROMOTER FOR INITIATION OF TRNASCRIPTION

REVERSIBLE MODIFICATIONS OF HISTONES

ACETYLATION CREATES WEAKER INTERACTION BETWEEN HISTONE(+) AND DNA (-)

LYSINE IN HISTONE --> HAT --> ACETYL-LYSINE RESIDUES IN HISTONE. HDAC REVERSES

(1) BIND DISITALLY FROM DNA PROMOTER

(2) MODULATE EFFICIENCY OF INITIATION (ENHANCER)

3) MEDIATE SIGNAL RESPONSE (e.g. HORMONE RESPONSE)

(4) REGULATE GENE EXPRESSION (TIME-DEPENDENT, TISSUE SPECIFIC)

(5) CAN ACT AS CO-ACTIVATORS RESULTING IN ENHANCEMENT

BINDING TRANSCRIPTION FACTORS TO PROMOTER. 2 PROMOTERS WITHIN TRANSCRIBED GENE.

BINDING OF POL III

PROCESSING OF tRNA PRECURSOR (REMOVING INTRONS)

POST-TRANSCRIPTIONAL MODIFICATIONS. TRINUCLEOTIDE SEQUENCE 'CCA' ADDED TO 3' END

BINDING OF TRANSCRIPTION FACTORS TO PROMOTERS LOCATED ON 2 DIFFERENT GENES (5.8 18 28 SEQUENCE AND 5 SEQUENCE)

TRANSCRIPTION TO MAKE rRNA PRECURSERS

REMOVING INTRONS FROM PRECURSERS

POST-TRANSCRIPTIONAL MODIFICATIONS (METHYLATION)

BINDING OF RIBOSOMAL PROTEINS TO FORM THE 2 SUBUNITS (40 & 60)

RECOGNITION OF UPSTREAM CIS-ACTING ELEMENTS (PROMOTERS & ENHANCERS)

BINDING OF TRANS ACTING ELEMENTS (TRANSCRIPTION FACTORS)

BINDING OF RNA POLYMERASE

CANNOT INITIATE TRANSCRIPTION WITHOUT PROMOTER

FUNCITON ONLY WHEN LOCATED ON THE SAME DNA MOLECULE AS PROMOTER THEY AFFECT

CAN FUNCTION AT GREAT DISTANCE FROM THEIR PROMOTER AND IN EITHER ORIENTATION

BINDING SITES FOR ENHANCER OR SILENCER PROTEINS (TRANS-ACTING ELEMENTS OR TRANSCRIPTIONAL TRANSACTIVATORS)

CORE PROMOTER SEQUENCES OR PROXIMAL ELEMENTS DETERMINE PRECISELY WHERE TRANSCRIPTION WILL INITIATE (TATA BOX 25 BP UPSTREAM OF START SITE)

UPSTREAM PROMOTER ELEMENTS ARE GENERALLY FIXED WITH RESPECT TO POSITION NEAR START SITE (CAAT BOX)

PROKARYOTES -- CLUSTERED RELATIVELY CLOSE TO START SITE. AT-RICH SEQUENCE AT -7 TO -10 BINDS SIGMA FACTOR WHICH IS IMPORTANT FOR RNA POL BINDING

EUK -- TATA BOX BINDING PROTEIN (TBP) IS PART OF LARGE TRANS-ACTING COMPLEX CALLED TFIID.

TBP OF THE TFIID BINDS TO TATA BOX, THEN RNA POL II AND BASAL TRANSCRIPTION FACTORS (TAFs) CREATING BASAL COMPLEX.

OTHER TAFs BIND TO STABILIZE THE BASAL COMPLEX (e.g. HELIX TURN HELIX AND ZINC FINGERS)

REGULATORY TRANSCRIPTION FACTOR FOR EUK

2 ALPHA HELICES SEPARATED BY BETA TURN.

ONE BINDS TO SPECIFIC DNA SEQUENCE AND THE OTHER INTRACTS WITH OTHER TFs

REGULATORY TRANSCRIPTIONFACTOR IN EUK

ONE OR MULTI MOTIFS WITH ZINC ATOM LINKED TO 2 CYSTEINE RESIDUES AND 2 HISTIDINE SIDE CHAINS

MOTIF FLANKED BY AN ALPHA HELIX AND A BETA SHEET. HELIX BINDS TO TARGET SEQUENCE

REGULATORY TRANSCRIPTION FACTORS IN EUK

ALPHA HELIX CONTAINING AT LEAST 4 LEUCINE RESIDUES WHICH ALIGN ON ONE EDGE

BINDS WITH ANOTHER LEUCINE HELIX VIA HYDROPHOBIC INTERACTIONS

DIMER FORMED (HOMO OR HETERO) AND BASIC SIDE HELIX ADJACENT TO ZIPPER BINDS TO DNA

REGULATORY TRANSCRITION FACTOR IN EUK TRANSCRIPTION

ONE DNA BINDING HELIX AND TWO DIMERIZED HELICES SEPARATED BY A NON-HELICAL LOOP

CONSISTS OF PROMOTER, OPERATOR, REPRESSOR (SEPARATE GENE), AND 3 STRUCTURAL GENES

REPRESSOR BINDS TO OPERATOR AND BLOCKS RNA POL IN THE ABSENCE OF LACTOSE

IF LAC IS PRESENT AND GLUCOSE IS DEPLETED, LAC CONVERTED TO INDUCER (ALLOLACTOSE) WHICH INACTIVATES REPRESSOR AND STARTS SYNTHESIS OF cAMP

cAMP BINDS TO CRP, WHICH BINDS TO REGULATORY SEQUENCE

RNA POL BINDS AND TRANSCRIPTION OCCURS

ALBUMIN GENE IN LIVER MODULATED BY TFs

LIVER PROTEIN TRANSTHYRETIN (PREALBUMIN) ACTS AS TF SPECIFIC TO HEPATOCYTES

NEURODEGENERATIVE DISEASES IN PRE-mRNA (POMA PARANEOPLASTIC NEUROPATHIES DUE TO MUTATION IN hnRNP-P2 WHICH BINDS TO PRE-mRNA)

COLORECTAL CANCER

INSULIN-LIKE GROWTH FACTOR 1 DEFICIENCY

SCID

• ALPH/BETA THALASSEMIA FROM REDUCED GLOBIN CHAIN SYNTHESIS. MAJOR DEFICIENCY CAUSES
• CHRONIC ANEMIA. TREAT BY BLOOD TRANSFUSION AND IRON CHELATION WITH DEFEROXAMINE

• THROMBOPHILIA (HYPERCOAGULABILITY) INCLUDING DVT AND
• PULMONARY EMBOLISM PE)

snRNPs BASE PAIR WITH THE 5’ SPLICE JUNCTION AND SEQUENCE WITHIN INTRON TERMED THE BRANCH POINT (ENTIRE COMPLEX CALLED SPLICEOSOME)

5’ END IS GU AND 3’ END IS AG

2’, 5’-PHOSPHODIESTER LINKAGE BETWEEN EXON 1 AND INTRON CALLED LARIAT.

EXON 1, INTRON, AND EXON 2 JOIN AND INTRON/snRNP RELEASED

DISORDER OF SPLICING CHARACTERIZED BY DEGENERATION OF SEVERAL TISSUES AND ORGANS INCLUDING SKIN, JOINTS, KIDNEYS, AND NERVOUS SYSTEM

CONTAIN ANTIBODIES TO SELF snRNP INHIBITING RNA SPLICING (AUTOIMMUNE DISEASE)

DEFECT IN ALTERNATIVE SPLICING CAN CAUSE BREAST AND OVARIAN CANCER

INVOLVED IN DNA DAMAGE REPAIR

ALTERING DEGRADATION OF mRNA ALSO REGULATES mRNA LEVELS

Ex, TRANSFERRIN RECEPTOR – WHEN IRON INSIDE CELL IS LOW THEN TRANSFERRIN RECEPTOR INCREASES. LACK OF IRON CAUSES IRE-BP TO BIND TO 3’UTR AND PROTECT TRANSFERRIN RNA FROM DEGRADATION

MUTATIONS IN IRON RESPONSE ATTRIBUTED TO MITOCHONDRIAL AND METABOLIC DISORDERS

TUMORS, BURKITT LYMPHOMA CAUSED BY TOO-STABLE Myc RNA WHICH IS A TRANSCRIPTION FACTOR

ADDITION OF A RESIDUES ON 3’ END OF VIRAL MRNA PROLONGS STABILITY (ex MEASLES & MUMPS)

CHANGES IN BASE-PAIR SEQUENCING CAN CAUSE MAJOR MODIFICATIONS IN ORF (ex Apo B USED TO PRODUCE 2 TISSUE-SPECIFIC PROTEINS (LIVER & INTESTINE)

REGULATE THE STABILITY OF MRNA

PRODUCED AS pre-miRNA THEN EXPORTED TO CYTOPLASM WHERE CLEAVED BY RNase TO MAKE SMALL 2X-STRANDED RNA

2X-RNA DISSOCIATES INTO siRNA WHICH HYBRIDIZES TO TARGET MRNA FORMING A SILENCING COMPLEX (RISC) CAUSING DEGRADATION

IF NOT HYBRIDIZED EXACTLY, TRANSLATION IS JUST INHIBITED

MAY BE INVOLVED IN ALZHEIMERS, PARKINSONS, AND SUSTAINED CARDIAC HYPERTROPHY

• ACTINOMYCIN D & ADRIAMYCIN (DOXORUBICIN), CANCER CHEMOTHERAPY. INHIBITS BOTH DNA
• REPLICATION AND RNA TRANSCRIPTION. HIGHLY TOXIC

ALPHA-AMANITIN, FROM POISONOUS MUSHROOMS INHIBITS EUK RNA POL II AND LESSER EXTENT POL III

RIFAMPICIN AND RIFAMYCIN B, INHIBIT ELONGATION BY BACTERIAL POL. TREATS INFECTION SUCH AS TB

Topoisomerase inhibitors: Camptothecin – inhibits human topoisomerase I by blocking the ligation of the DNA breaks made by the enzyme

DNA Pol Inhibitors: Arabinosyl cytosine (AraC, cytosine arabinoside) Chain terminator: lacks a reactive 3’ OH so chain elongation stops when DNA Pol incorporates it into the replicating strand

Agents that cross link strands: cisplatin

• §
• Novobiocin: inhibits bacterial topoisomerase (selective for bacteria)

• §
• Nalidixic acid: inhibits bacterial topoisomerase, treats MRSA and anthrax

Reverse Transcriptase inhibitors:

• Azidodeoxythymidine (AZT) and 2’,’3-dideoxycytidine (DDC)
• Lack reactive OH’s so they stop chain elongation
• Combined with other drugs for HAART (highly active retroviral therapy)
• Have preferential affinity for RT and less for the host cell’s DNA polymerase

Efavirenz – non-nucleotide RT inhibitor (NNRTI) – binds allosteric site to distort the catalytic asp residues and make RT nonfunctional

• Acyclovir – used to block Herpes virus (HSV)
• PO’d to monophosphate form by VIRAL thymidine kinase, then to di- and tri-
• PO’d nucleotide is incorporated and acts as chain terminator
• Specific only for the VIRAL kinase….very little side effects if HSV is not present