Title:
Human Repetitive DNA Sequences as a Source of Chromosomal Fragility and Genome Rearrangements in Yeast: Implications for Human Polymorphisms and Diseases
Human Repetitive DNA Sequences as a Source of Chromosomal Fragility and Genome Rearrangements in Yeast: Implications for Human Polymorphisms and Diseases
No Thumbnail Available
Author(s)
Lobachev, Kirill
Advisor(s)
Editor(s)
Collections
Supplementary to
Permanent Link
Abstract
Eukaryotic chromosomes must be accurately maintained, duplicated and segregated during mitotic and meiotic divisions to
guarantee inheritance of the correct genetic information by the daughter cells. However, occasionally genome integrity can
be compromised: chromosomes break and rearrange which can cause drastic changes in the way how genes are expressed.
This type of genetic instability is a causative factor in the development of many hereditary diseases and cancers in humans.
On the other hand, the ability of chromosomes to undergo breakage and rearrangements promotes genetic variations that
contribute to species polymorphisms and evolution. Multiple environmental and intracellular factors such as ionizing
radiation, UV light or reactive oxygen species are well-established damaging agents that can fracture chromosomes at any
position and trigger chromosomal abnormalities. Nevertheless, work over recent years has established that breaks along the
chromosomes do not occur randomly but rather often coincide with the regions containing repetitive elements capable of
adopting non-canonical DNA secondary structures. The enigmatic discovery that DNA repeats which can be inherited or
occur de novo are a very powerful source of the breakage and rearrangements adds new perspective to our understanding of
the origin of human pathology, polymorphism and evolution. Why breaks happen, what genetic and environmental factors
contribute to fragility, what are the consequences of these types of breaks for the integrity of the eukaryotic genome? Those
are the questions that we are trying to address using yeast as a model eukaryotic organism in my laboratory. I will present
our new findings related to three sequence motifs that can adopt different secondary structures. The underlying mechanisms
of repeat-mediated breakage uncovered in yeast can be extrapolated to the studies of chromosomal dynamics of higher
eukaryotes including humans.
Sponsor
Date Issued
2010-02-16
Extent
56:24 minutes
Resource Type
Moving Image
Resource Subtype
Lecture