Overview

Answers to the self-test quiz which you are supposed to do BEFORE the lecture:

1. The short answer - a very long time. About 2.4x10¹² years.
     That's about 160 times longer than the estimated age of the universe!

2. The piece of paper would be quite thick - it would reach outside the earth's
     atmosphere and beyond the orbit of the planet Mars.

Link to last year's introductory lecture

Part 2: DNA Symmetry Elements and DNA Structures

Background:

Introduction to DNA symmetry elements

DNA is like Coca-cola

Historical background - fiber diffraction vs. X-ray crystallography

Families of DNA helices

A Brief Introduction to Alternative Conformations of DNA

DNA symmetry elements defined

From a DNA sequence perspective, there are 4 types of repeats:

Direct Repeats

Simple Tandem Repeats

(Longer)Tandem Repeats

Direct (non-tandem)

Phased Repeats

Inverted Repeats



Mirror Repeats




Everted Repeats

On the "Biological Meanings" of Symmetry Elements

Anatomy of chromosomes - there are four important parts in metaphase chromosomes (telomeres, centromeres, and heterochromatin & euchromatin):

Figure 6.20b from Hartl & Jones, "GENETICS - Principles and Analysis", fourth edition (1998).

There are two types of chromatin:

Heterochromatin - where the DNA is more condensed, and usually there is not much transcriptional activity.  Some heterochromatin will remain condensed throughout the cell cycle.

Euchromatin - this is where the "active" genes are - usually this region is much less condensed.

Centromeric DNA

Figure 6.25 from Hartl & Jones, "GENETICS - Principles and Analysis", fourth edition (1998).

There are certain DNA sequences that are associated with the centromeres of chromosomes. Knowledge of this was essential in the construction of Yeast Artificial Chromosomes (or YACs, as they're usually called).

Figure 6.15 from Hartl & Jones, "GENETICS - Principles and Analysis", fourth edition (1998).

Here's an oversimplified view of the attachement of the kinetochore, which consists of several hundred microtubles bound together.

Telomeric DNA

telomeric DNA can fold back on itself. This is necessary to allow for DNA synthesis (this isn't a problem for circular chromosomes!).

The ends of the chromosomes gets shorter every time the cells divide, because part of the bases are used to template off of themselves. Thus, after every round of replication, the chromosome gets a bit shorter. This is kind of like "planned obscelence", where the cells basically have so many divisions and then they fall apart. However (fortunately!) the cells have a mechanism for extending the length of the telomeres - the name of the enzyme is TELOMERASE. It has been found that in many cases cancer cells have a mutation such that the telomerase gene is overexpressed, thus allowing the cells to "live forever". Early results from clinical trials show that by specifically inhibiting the activity of the telomerase protein, they can slow or completely stop the growth of many types of cancer. More recently, the idea of using telomerase gene therapy to prevent people from getting old has received much attention in the media.

Figure 6.26 from Hartl & Jones (page 250).

Repetitive DNA

Highly repetitive DNA

Dispersed - e.g., Alu family

 about 300 bp long
 500,000 copies in humans
 (about 5% of the human genome)
 dispersed throughout the chromosomes

Localised highly repetitive sequences

about 2-10 bp long
 present in millions of copies, often in large blocks
 (about 6% of the human genome)
 associated with heterochromatin
 usually very high A+T content

Middle repetitive DNA

 makes up more than 40% of the human genome
 position varies due to transposable elements

 Includes the following types of sequences:

microsatellite DNA

Dinucleotide repeats

Trinucleotide repeats
      - associated with many diseases (e.g., Fragile X, muscular distrophy)

Table of DNA sequences, structures, and biological functions

Sequence motif	Possible structure	Biological function
(C3TA2)n	4-stranded DNA	Telomeres
(ACA5GAGTGT3CA2...)n	Curved DNA	associated with Centromeres (171 bp alphoid repeat)
(A3-5N5-7)n	Curved DNA	promoter regions
(R)n, where n > 250 bp	A-DNA stable intramolecular triplex DNA	transposons homologous recombination
(ttcca)n, where n ~ 1,000,000 bp	A-DNA stable intramolecular triplex DNA	human y chromosome
(RY)n	Z-DNA (>50% GC rich) Cruciforms Slipped-mispair	induce mRNA editing deletions (in bacteria) mutagenesis
+   (N)n	recA triple-stranded DNA	homologous recombination
+   (R)n	Intermolecular triplex Intramolecular Triple-strands	recombination replication
+ (N)n	cruciforms	deletions (in bacteria) insertion sequences
+ (N)n	parallel stranded DNA	unknown stabilisation of telomeres(?)

---

References:

Sinden,R.R., Pearson,C.E., Potaman,V.N., Ussery,D.W., "DNA: STRUCTURE and FUNCTION", Advances in Genome Biology, 5A:1-141, (1998).

Calladine,C.R., Drew,H.R., "Understanding DNA: The Molecule and How It Works", (2nd edition, Academic Press, San Diego, 1997).

References on DNA

---

LINKS:

"Official" CBS Bioinformatics links
(an on-line and updated version of Chapter 12 from the Baldi & Brunak book)

HMS Beagle report on NCBI Bioinformatics sites - this is a good place for a molecular biologist to start!

The Human Genome Project Information page - this is put out by Los Alamos National Labs, and is updated regularly.

---

Back to the CBS homepage

Back to Dave's Courses page

Last modified Tuesday, 28 September, 1999 by David Ussery