Biochermistry Review (unfinished)

AZT-deoxythymidine analog

HIV’s reverse transcriptase has a higher affinity for AZT triphosphate than for dTTP, and binding of AZT triphosphate to this enzyme competitively inhibits

dTTP binding. When AZT is added to the 3_ end of

the growing DNA strand, lack of a 3_ hydroxyl means

that the DNA strand is terminated prematurely and

viral DNA synthesis grinds to a halt.

Methotrexate is

is an inhibitor

of dihydrofolate reductase. This folate analog acts as a

competitive inhibitor; the enzyme binds methotrexate

with about 100 times higher affinity than dihydrofolate.

Cytidine cCMP a ribonucleotide Lehninger p.294

In eukaryotic cells, about 5% of cytidine residues in DNA are methylated to 5-methylcytidine (Fig. 8–5a).Methylation is most common at CpG dinucleotides sequences, producing methyl-CpG symmetrically on both strands of the DNA. The extent of methylation of CpG sequences varies by molecular region in large eukaryotic DNA molecules. Methylation suppresses the migration of segments of DNA called transposons, described in Chapter 25.

DNA methylation occurs mainly at CpG dinucleotides that often cluster in at the upperstream promoter regions of genes (CpG islands). While these are generally correlated with gene inactivation, there are many exceptions. Double crossovers at meiosis can substitude a normal allele for a mutant allele (conversion), and reverse transcriptases can copy intronless mRNA into complementary DNAs(cDNA) that integrate into the genome as psueudogenes. Immunoglobulin genes undergo gene rearrangement to unite variable, joining, and constant regions fro expression of a unique antibody. Unequal crossing over between sister chromatids is thought to be an important mechanism for variation in copy number within gene clusters

Skin cancer: Lehninger p. 970

UVB causes extra covalent bond between two neighboring pyrimidines in the same strand => dimer formation => normal DNA replication interrupted => non complementary base added => removed by excision repair system

Nucleotide-excision repair is the sole repair

pathway for pyrimidine dimers in humans, people with

XP are extremely light sensitive and readily develop

sunlight-induced skin cancers. Most people with XP

also have neurological abnormalities, presumably because

of their inability to repair certain lesions caused

by the high rate of oxidative metabolism in neurons.

Defects in the genes encoding any of at least seven

different protein components of the nucleotide excision

repair system can result in XP, giving rise

to seven different genetic groups denoted XPA to

XPG. Several of these proteins (notably XPB, XPD,

and XPG)

Tag: skin cancer, DNA repairment,

RFLP (Restriction fragment length polymorphism) Lehninger p.322

Detecting method: Southern blotting

Augmentation : PCR

Application : Crime investigation, Paternity identification, by DNA fingerprinting

Miscellaneous: inheritance disease detection: only when the mutant site is at or closely linked to an altered restriction site

Tag : RFLP DNA fingerprinting

Telomere:

Okazaki fragment:

The pieces during DNA replication in the lagging strand ( 3’-> 5’). All polymerases and repair enzyme only work 5’->3’. Okazaki fragments are not exceptional. They are the 5’->3’ little strands but grossly in 3’->5’ direction. They are combined by DNA ligase.