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40 SECTION II BIOCHEmISTRY ``BIOCHEMISTRY—MOlECUlAR BIOCHEmISTRY ``BIOCHEMISTRY—MOlECUlAR
Lac operon Classic example of a genetic response to an environmental change. Glucose is the preferred
metabolic substrate in E coli, but when glucose is absent and lactose is available, the lac operon is
activated to switch to lactose metabolism. Mechanism of shift:
Low glucose adenylate cyclase activity generation of cAMP from ATP activation of
catabolite activator protein (CAP) transcription.
High lactose unbinds repressor protein from repressor/operator site transcription.
CAP
Genes
Adenylate Lacl site P O LacZ LacY LacA
CAP cAMP cyclase Glucose DNA 5 3
AUG AUG AUG
Messenger RNA
Binds CAP site, ATP
induces transcription RNA
Lac operon STATE CAP polymerase
Low glucose
Lactose available
Lac genes strongly expressed
Lacl CAP site Promoter Operator LacZ LacY LacA
Repressor protein
High glucose
Binds operator, Lactose unavailable Lac genes not expressed
blocks transcription
Low glucose
Repressor Lactose unavailable Lac genes not expressed
protein CAP
High glucose site P O
Lactose available Very low (basal) expression
Allolactose Inactivated
(inducer) repressor
DNA repair
Single strand
Nucleotide excision Specific endonucleases release the Defective in xeroderma pigmentosum (inability
repair oligonucleotides containing damaged bases; to repair DNA pyrimidine dimers caused by
DNA polymerase and ligase fill and reseal the UV exposure).
gap, respectively. Repairs bulky helix-distorting Findings: dry skin, extreme light sensitivity, skin
lesions. Occurs in G 1 phase of cell cycle. cancer.
Base excision repair Base-specific Glycosylase removes altered base Important in repair of spontaneous/toxic
and creates AP site (apurinic/apyrimidinic). deamination.
One or more nucleotides are removed by “GEL PLease”
AP-Endonuclease, which cleaves 5′ end.
AP-Lyase cleaves 3′ end. DNA Polymerase-β
fills the gap and DNA Ligase seals it. Occurs
throughout cell cycle.
Mismatch repair Mismatched nucleotides in newly synthesized Defective in Lynch syndrome (hereditary
(unmethylated) strand are removed and gap is nonpolyposis colorectal cancer [HNPCC]).
filled and resealed. Occurs predominantly in S
phase of cell cycle.
Double strand
Nonhomologous end Brings together 2 ends of DNA fragments to Defective in ataxia-telangiectasia.
joining repair double-stranded breaks. No requirement for homology. Some DNA may
be lost.
Homologous Requires 2 homologous DNA duplexes. A Defective in breast/ovarian cancers with BRCA1
recombination strand from damaged dsDNA is repaired mutation and in Fanconi anemia.
using a complementary strand from intact Restores duplexes accurately without loss of
homologous dsDNA as a template. nucleotides.
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