chromatin structure and replication1 chromosome structure and replication from chapters 5 & 6...
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Chromatin Structure and Replication 1
Chromosome Structure and Replication
From chapters 5 & 6
Chapter 5While we will not cover DNA structure in class formally, but you should review materials in the chapter on the fundamental structures of DNA. We will discuss in class chromatin structure covered on pages pp 184-192.
In Chapter 6, you will not be responsible for the details of homologous recombination.
Questions in this chapter you should be able to answer:Chapter 5- #s 1, 3, 4, 5A& B, 7, 11-14, 16Chapter 6- #s 1 - 8, 12 -16
DNA Helicase
Chromatin Structure and Replication 2
From Chapter 5Eukaryotic DNA exists as chromatin
Chromatin = DNA + histones
Nucleosome core
Histone octet
H1Nucleosome
Chromatin Structure and Replication 3
Nucleosomes allow for DNA condensation and “remodeling”
Histone modifications
Hetero- & Euchromatin
DNA supercoiling
“Inheritable”
Supercoiling
Chromatin Structure and Replication 4
From Chapter 6Why is DNA replication said to be ‘semiconservatve’?
Read How We know about Meselson and Stahl experiment
Chromatin Structure and Replication 5
In what direction does DNA replication occur?
Where does energy for addition of nucleotide come from?
What happens if a base mismatch occurs?
DNA Orietation
Chromatin Structure and Replication 6
Why does DNA replication only occur in the 5’ to 3’ direction?
(Picture not in 4th edition)
Chromatin Structure and Replication 7
1) How many nM / mM?2) How many nM between 4 - 5?3) How many bases between 4 – 5?4) How long to replicate this region?
Answer Question 6-1AHow long until forks 4 and 5 meet?Distance between bases is 0.34 nmReplication rate is 100 bases / sec
Where does DNA replication begin on a chromosome?
Chromatin Structure and Replication 8
How is DNA synthesized on 3’ end‘behind’ advancing replication fork?
Okasaki fragments
Chromatin Structure and Replication 9
Why does DNA synthesis begin with an RNA primer?
How are Okasaki fragmentssynthesized and connected?
Chromatin Structure and Replication 10
How do other proteins contribute to DNA replication?
HelicaseTopoisomerasessDNA binding proteinsSliding clampDNA PolymerasesLigase
DNA Replication
Replication Fork
Chromatin Structure and Replication 11
What is the telomere replication problem?
The telomere replication problem
On the 3’ ends
Telomeres and aging and cancer
Chromatin Structure and Replication 12
How does telomerase solve the problem??
RNA template
Telomerase and cancer treatment
Telomere Replication
Chromatin Structure and Replication 13
How is damaged DNA repaired?
Surveillance & repair proteins
1) Mismatch repair during S-phase-- how does the cell know which base to replace?
2) Excision repair (mismatch)-- post S-phase-- 3 steps-- 50% chance of error
Chromatin Structure and Replication 14
How is damaged DNA repaired?
3) End-joining of DS breaks-- Nonhomologous end joining-- short deletion
4) Homologous recombination-- usually S-phase-- sequence on homolog is used
Gene & Genome Evolution 15
Mutations accumulate over time
Numerous single-nucleotide polymorphisms (SNP) distinguish individual genomes
Consequence of “point mutations”
107+ documented in humans
Can influence:Our individual physical traitsDisease susceptibilityRisk factors for disorders
e.g., Macular DegenerationSNP in Complement factor HHis Tyr5 – 7x >risk