nucleoside
- pentose bonded to a nitrogenous base, formed by covalently linking the base to C-1’ of the sugar
nucleotides
- one or more P groups are attached to the C-5’ of a nucleoside
- ADP and ATP
- building blocks of DNA
nucleoside~> nucleotides
~
Nucleoside Nucleotides
(deoxy)A (d)AMP (d)ADP (d)ATP
(deoxy)G (d)GMP (d)GDP (d)GTP
(deoxy)C (d)CMP (d)CDP (d)CTP
(deoxy)U (d)UMP (d)UDP (d)UTP
(deoxy)T dTMP dTDP dTTP
sugar phosphate backbone
- alternating sugar and phosphate backbone of DNA
- determines directionality
- always read from 5’ to 3’
- formed as nucleotides are joined by 3’ C of one sugar - 5’ phosphate group phosphodiester bonds
- DNA and RNA have negative charges overall because phosphates carry negative charge
purines
- contain two rings
- A and G
- aromatic
pyrimidines
- only one ring
- CUT
- U is RNA exclusive
- aromatic
aromatic
1) cyclic
2) planar
3) conjugated
4) 4n+2 pi electrons
- pi orbital overlap increases stability
watson and crick model
- two strands of DNA are anti parallel (oriented in opposite directions)
- sugar-P outside which nitrogenous bases inside
- complementary base pairing (AT 2 H bonds, GC 3 H bonds)
chargaff’s rule
- total purines equal total pyrimidines overall
B-DNA
- right-handed helix
- every ten bases a turn
Z-DNA
- zigzag
- left-handed helix 12 bases each turn
- no bio activity attributed to it
denaturation of DNA
- H bonding and base pairing disrupted
reannealing of DNA
- denaturing condition slowly removed
cancer cells migrate by local invasion or…
metastasis via bloodstream or lymphatic system
over time cancel cells accumulate…
mutations
oncogenes
- mutated genes that cause cancer
- primarily encode cell cycle-related proteins
- before gene mutation, known as proto-oncogenes
- irregular proliferation is dominant
antioncogenes
- tumor suppression
- inhibit cell cycle or participate in DNA repair process
- mutations of these genes therefore cause cancer
proofreading
- two double stranded DNA molecules will pass through a part of the DNA polymerase enzyme for proofreading
- incorrectly paired bases, unstable H bonding, detected as it passes through this part of polymerase
- incorrect base in excised and can be replaced with the correct one
- enzyme looks at level of methylation to discriminate template strand and incorrectly paired daughter strand: template strand has existed longer and is more heavily methylated
why is likelihood of mutations in the lagging strand higher than leading?
- DNA ligase lacks proofreading ability
mismatch repair
- cells also have machinery in the G2 phase of the cell cycle for mismatch repair
- enzymes detect and remove errors introduced in replication that were missed during S phase
- encoded by MSH2 and MLH1
when does nucleotide and base excision repair occur?
G1 and G2
nucleotide excision repair
- UV induces dimer formation between adjacent thymine DNA residues
- this interferes w DNA replication and normal gene expression, and distorts double helix
- NER eliminates them
1) proteins can the DNA and recognize lesion/bulge
2) excision endonuclease makes nicks in phosphodiester backbone of damaged strand on both sides of thymine, and removes the oligonucleotide
3) DNA polymerase fills in gap by synthesizing DNA in 5’ to 3’ direction, using undamaged strand as a template
4) nick strand sealed by DNA ligase
base excision repair
- repairs small non helix distorting mutations
1) affected base is recognized and removed by a glycosylase enzyme leaving behind AP site
2) recognized by AP endonuclease that removes damaged sequence from DNA
3) DNA polymerase and DNA ligase can then fill in the gap and seal the strand
