chromatin structure and replication1 chromosome structure and replication from chapters 5 & 6...

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