Lecture 21 Flashcards
Define transposable elements
Sequences that can move about the genome; make up about 45% human DNA, often cause mutations, able to insert at many different locations,
What is the basic structural organization of transposable elements?
Flanking direct repeats 3-12 bp long that don’t travel with the element and are regenerated at the point of insertion, terminal inverted repeats 9-40 bp long required for transposition to take place that are inverted and complementary on same strand
Describe mechanism for replicative transposition
- Single copy of transposable element is on one DNA molecule
- 2 DNA molecules are joined
- Transposable element is replicated, which results in production of a cointegrate structure (2 DNA molecules plus 2 copies of the transposable element)
- Crossing over at regions within the copies of the transposable element produces 2 molecules, each with a single copy of the transposable element = resolution of the cointegrate
Describe mechanism for nonreplicative transposition
- Cleavage requires a transposase enzyme produced by the transposable element
- Joining of transposable element is carried out by normal replication and repair enzymes
- Original site is typically repaired using homologous template on sister chromatid
Define retrotransposons
Elements that transpose through an RNA intermediate; RNA is transcribed from a DNA transposable element, RNA is copied back to another DNA site using reverse transcriptase; only done through replicative transposition; more common than DNA transposons in eukaryotes
What is the difference between replicative and nonreplicative transposition?
Main difference is that replicative transposition results in an increase in the number of copies of the transposable element and nonreplicative transposition does not increase the number of copies
Compare and contrast transposons in eukaryotes and prokaryotes
Prokaryotic: contain DNA transposons and consist of insertion sequences (carry only information for movement) and composite transposons (flanked by 2 copies of insertion sequence and contains sequences not directly related to transposition)
Eukaryotic: 2 groups, those structurally similar to transposable elements found in bacteria that typically end in short inverted repeats and transpose as DNA, and retrotransposons that are reverse transcribed into the DNA (similar to retroviruses)
Describe the role played by transposons in genome evolution
Can be thought of as genomic parasites that provide no benefit to the cell and may be harmful; may exist because they generate diversity
What are the consequences of transposons on human health?
Can lead to hemophilia, Menkes disease, cystic fibrosis, CHARGE syndrome, breast cancer, and Apert syndrome, among others
What potential role does p53 play in transposon contribution to cancer?
p53 is a tumor suppressor that sense and represses retrotransposons; p53 senses their movement and acts to restrain these mobile elements; when mutated, retroelement activity is dramatically increased, which can potentially drive tumorigenesis and other transposopathies (disease states linked to eruptions of mobile elements)
What is transposase and resolvase and what are they involved with?
Transposase: enzyme that binds to the end of a transposon and catalyzes the movement
Resolvase: enzyme which brings about the separation of 2 transposons contained in a cointegrate during the process of replicative transposition
Involved in replicative transposition
What are SINES and what are LINES?
SINES (short interspersed nuclear elements): constitute about 11% of the human genome (includes Alu)
LINES (long interspersed nuclear elements): constitute about 21% of the total human DNA; about 900,000 copies in the genome
