DNA Organization and Related Topics | Controls

DNA organization

Heterochromatin

This part of a chromosome's DNA content is not transcribed; in interphase, it is very dense (ex. Barr Body).  10% to 25% of DNA is short (5 to 10 bases) sequences that are repeated.

Euchromatin

This is transcribed; sometimes called "true chromatin."

Satellite DNA

In chromosomes, it is typically located at tips and centromeres having repetitive sequences.  Satellite DNA is a very dense material because of small repeats (ex. Fragile X Syndrome).

Telomeres

This is satellite DNA at tips of chromosomes (in humans the sequence TTAGGG).  Differentiate ultracentrifugation isolates satellite DNA.

What is this I hear about telomeres and age?

During replication, at the end of the lagging strand of DNA, it is impossible to add a primer; so instead of decreasing the lengh after each division, special repeating sequences (telomeres) are added on the end of each chromosome.  Telemere size is relative to age.

Multigene Families

These are collections of identical or very similar (according to nucleotide sequences) genes.
     e.g., alpha- and beta-globulins (hemoglobin subunits) are on different chromosomes and their corresponding gene versions are transcribed or expressed at different times.

Tandem Gene Duplication

Repeated gene duplication gives rise to mistakes in replication and recombination.  Evidence is pseudogenes.  Pseudogenes are sequences very similar but lack necessary sites (eg promoters) to be transcribed.

Controls

There are 5 known ways we regulate our genes:

transcriptional control similar to bacterial controls transcript processing control factor in the maturation of hnRNA (introns-exons) transport control RNA transport from nucleus to cytoplasm to ribosome some factor or selecting messenger translational control impact rate or start (inhibit initiation phase) post-translational control proteins must be conformed (possible inhibition) Transcriptional transcription factors and RNA polymerase bind to promoter another transcription factor binds to the enhancer regions of DNA (far away from sequencing) this stimulates the right complex to transcribe DNA the right complex is probably when a loop forms bringing the transcription factor attached to the enhancer in contact with the transcription factor binded to RNA polymerase

Transcript (RNA) processing and Export (little is known)

1. mRNA, tRNA, or rRNA?
2. mrNA needs a 5' cap and a poly-A tail and introl excision with exon splicing
3. exported
4. ribosome associations

mRNA degradation

The lifespan of mRNA can be days, hours, or weeks but is most often minutes.  Proteins that bind to mRNA and block translation also block degradation.  The length of the poly-A tail also affects degradation; the longer it is the longer degradation takes to occur.

Translational Summary

1. protein attachement to 5' ends of messages hinder ribosome attachment
2. translation of all mRNA can be stopped by inactivating initiation factors

Post-Translational Summary

Protein processing

1. modification
2. conformation
3. transportation

Coordinated Control (on and off simultaneously)

in eukaryotes:	no operon with sequential genes have been found. genes coding for sequential enzymes in a metabolic process are scattered around different chromosomes.
examples:	1.  set of proteins induced after high temperature 2.  transcription changes from steriod hormones 3.  during cellular differentiation

Differentiation occurs as a result of presence/absence of tissue-specific proteins.  Cell contents and position in the embryo determine differentiation by activating transcription factors.

Chemical signals control gene expression in insects.  A puff (puffs) or Lampbrush chromosomes occur when DNA loops out from the axis (decondenses) perhaps making it more aailable for transcription.

Gene Expression in vertebrates

e.g. a noncompetitive hormone enters receptor protein at other than active site causing competitive inhibitor to be released freeing up DNA binding surface so that the protein can bond to an enhancer region to stimulate transcription.  Non-steroids must bind to a recepter on the ECM and send message via signal transduction pathways.

Immunoglobulins are antibodies made by B-lymphocytes - an unspecialized cell - by piecing together random antibody genes from several DNA regionsn separated in embryonic development.

DNA methylation

Inactive DNA is usually highly methylated (e.g. 5% of cytosine bases are methylated).

A review of oncogenes and proto-oncogenes:

oncogenes

proto-oncogenes

are cancer causing genes

have the potential to cause cancer but need some alteration to become oncogenes 4 active ways to do that: gene amplification:  "too much of a good thing." gene transposition:  move it to a more actively transcribed or more-likely-to-be-transcribed area on a chromosome. chromosome translocation: (see #2.) point mutation: make a hyperactive or degradation-resilient protein. another (indirect) way... alter tumor-repressor genes (genes that make proteins to prevent mitosis)

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