molecular basis of inheritance

who began discovery of the genetic role of DNA for evidence of DNA can transform bacteria

F. Griffith

what did griffith work with

2 strains of bacterium; pathogenic (S strain) + harmless (R strain)

what’s the phenomenon of mixing heat-killed remains of S strain w/ living cells of R strain = some living became pathogenic

transformation → bacteria capable of transferring genetic material

who showed that DNA is genetic material of a phage known as T2; showed only 1 of 2 components of DNA/Protein enters an E. coli cell during infection; concluded injected DNA of the phage provides genetic information

A. Hershey & M. Chase

what are Chargaff rules

base composition of DNA varies between species; evidence of diversity made DNA more credible candidate of genetic material; any species # of A=T bases & # of G=C bases; not understood till discovery of double helix

what technique did M. Wilkins + R. Franklin use to study molecular structure of DNA

X-ray crystallography

built double helix to conform DNA and found the backbones were antiparallel

Watson + Crick

why do purines (A/G) pair with pyrimidines (C/T/U)

for uniform width consistent w/ X-ray data

which way is DNA read and formed/synthesized

read → 3’ to 5’ and formed 5’ to 3’w

what did Watson+Crick semiconservative model predict

one old strand and one new strand

whats a conservative model

two parent strand rejoin

whats a dispersive model

each strand a mix of old and new

where does replication begin and how many sites are there for eukaryotic chromosomes

replication bubble and have multiple origins; replication proceeds in both directions of origin

describe prokaryotic replication

• small genomes

• 5000 genes

• 1 origin

• 1-2 types polymerases

• faster

  • no ends to synthesize

describe eukaryotic replication

• large range → more DNA

• C value paradox. intron-exon shuffling

• multiple origins

• 4+ types of polymerases

• slower

  • telomere replication distincitve

amount of DNA/haploid cell not correlated w/ evolutionary complexity

C value paradox

what do helicases do

untwist the double helix at replication forks

what do single stranded binding proteins do

bind to and stabilize single stranded DNA

what do topoisomerase do

relieves strain of twisting of double helix by breaking, swiveling, rejoining DNA strands

what is the primer for DNA polymerases to add nucleotides

RNA primer which is synthesized by primase

what end serves as the starting point for new DNA after the primer

3’ end

what do DNA polymerases do

catalyze synthesis of new DNA at replication fork

what’s the differnece between dATP and ATP sugars

dATP = deoxyribose, ATP = ribose

how does monomer join DNA strands to lose 2 phosphate groups

dehydration reaction

what end does DNA polymerases add nucleotides to a growing strand and new DNA strand elongates only in what direction

free 3’, 5’ to 3’

what does DNA pol III do

synthesizes leading strand continuously towards replication fork

what direction does DNA pol have to work in for the lagging strand

direction away from replication fork

how is the lagging strand synthesized

series of segments → Okazaki fragments joined by DNA ligase

in bacterial DNA replication what does the sliding clamp do

holds DNA pol in place when nucleotides are addedw

what does DNA pol II do in bacterial DNA

repair

what’s the trombone model

lagging strand forms loop that leading strand/lagging strand contact one another

repair enzymes correct errors in base pairing

mismatch repair

how can DNA be damages

harmful chemica/physical exposure; spontaneous change

an endonuclease cuts out + replaced damaged stretches of DNA

nucleotide excision repair

what are evolutionary significance of alter DNA

• error rate → low but not zero

• sequence changes may be permanent

  • mutations source of genetic variation

what’s the limitation of linear DNA chromosomes

no way to complete 5’ ends → more rounds of replication = shorter DNA w/ uneven ends (no problem for prokaryotes which are circular chromosomes)

what are the special nucleotide sequences at their ends in eukaryotic chromosomal DNA

telomeres (non-coding)

what happens if chromosomes of germ cells become shorter

essential genes would be missing from gametes produced

what do telomeres do

postpone erosion of genes near DNA end, protect ends of chromosomes from deterioration, ensure genetic info passing, TTAGGG

ribonucleoprotein, carries own RNA → CCCAAUCCC, adds telomere repeat TTAGG to 3’ end

telomerase

treat aging / age related diseases

telomerase activation

treat cancer

telomerase inhibition