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Gene Rearrangements
Medical School Biochem
19
Biochemistry
Graduate
08/20/2011

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Term
What is the heteroduplex joint?
Definition
The point where strands from two different DNA helices have based paired
Term
Why is homology important in homologous recombination
Definition
pieces of the chromosome have to be nearly identical for a good heteroduplex joint to form
Term
What is the mechanism of homologous recombination?
Definition
1. Double Strand Break
2. Nucleases degrade open ends to make 3' ends
3. Sticky ends find homologous part of and intact chromosome forming a D (displacement) loop.
4. DNA synthesis to repair parts of chromosome degraded by nucleases
5. Pairing of other ends (this is the formation of the Holliday Junction)
6. Strand cutting resulting in either crossing over or the return of the chromosome to previous state
Term
Crossing over during a Holliday junction happens predominantly in which type of cell division?
Definition
Meiosis
Term
What is the mechanism of gene conversion?
Definition
after homologous recombination sometimes the heteroduplex joint is so poor that DNA repair machinery ends up rewriting a section of DNA resulting in gene conversion
Term
What is gene conversion?
Definition
conversion of a sequence of genes on a chromosome to the genes of its homologous pair
Term
What is the clinical significance of DNA-only transposons?
Definition
In many bacteria this is the mechanism by which drug resistance is passed
Term
Why does a transposon need to have short inverted repeat sequences on either end of its code?
Definition
This is the way that transposons are recognized by active transposase complex
Term
What is the complex that excises and reintegrates DNA transposons?
Definition
active transposase complex
Term
What is the mechanism of Cut-and-paste transpositions (DNA-only transposons)
Definition
1.active transposase complex recognizes transposon via the end sequences and excises the transposon
2. The transposase then finds a target chromosome and inserts the transposon
Term
What is the enzyme used by retroviruses to synthesize DNA?
Definition
reverse transcriptase
Term
What is the life cycle of a retrovirus?
Definition
1. Invasion into a cell, loss of envelope
2. Reverse transcriptase makes DNA single strand, single strand gets polymerized into a double strand
3. Integration of DNA copy into host chromosome
4. transcription and translation yield many copies of viral RNA, reverse transcriptase, and necessary transport proteins
5. Virions assemble and burst out of the cell to infect new cells
Term
What is integrase?
Definition
Integrase is a functional analog to transposase. It is an enzyme used in the integration of human endogenous retroviruses into a gene sequence
Term
What is the mechanism of Human Endogenous Retroviruses?
Definition
Same mechanism as retroviruses except that the integrated DNA does not code for virions that then rupture the cell.

Integrase is the enzyme that integrates the trascripted DNA into the new chromosome
Term
How many active Human endogenous retroviruses exist in the human genome?
Definition
~50
Term
What is the clinical relevance of human endogenous retroviruses?
Definition
HERV proteins have been correlated with human melanoma cell lines and tissues.

offers potential diagnostics and prognistic data
Term
What is the mechanism of nonretroviral retrotransposons?
Definition
1. RNA code is synthesized from DNA
2. Reverse Transcriptase and Endonuclease is either synthesized from the RNA code or found natively in the cell.
3. Endonuclease cleaves target DNA and lines up RNA
4. Reverse transcriptase uses RNA to synthesize DNA into the target chromosome
5. multi-step pathway produces second DNA strand
Term
What is the difference between LINEs and SINEs?
Definition
SINEs do not have sufficient genetic code to code for the enzymes (endonuclease and reverse transcriptase) it needs so it must find them natively in the cells
Term
What percent of the genome is made of actively coding genes?
Definition
1.5%
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