Structural Aberrations: Introduction Flashcards
_____ result from chromosomal breakage and abnormal reunion but they can be induced experimentally by ionising radiation and mutagenic agents.
Structural aberrations
Defective DNS repair system for double stranded breaks is associated with inactivation of _____.
breast cancer-related BRCA1 protein
T/F. When a chromosome breaks, two unstable sticky ends without telomeres are pro- duced. Generally, repair mechanisms rejoin these two ends without delay. However, if more than one break has occurred, or if the double-strand break DNA repair system is defective then, as the repair mechanisms cannot distinguish one sticky end from another, there is the possibility of rejoining the wrong ends.
True.
The spontaneous rate of chromosomal breakage is markedly increased by exposure to _____, either environmental or therapeutic, and is also increased in some rare inherited conditions such as _____.
ionising radiation; Fanconi anaemia.
X-rays produce ____ at any stage of the cell cycle in a _____ fashion, but without any increase in the number of sister chromatid exchanges. In contrast, chemical mutagens, which are _____, induce ____ rather than chromatid break and exchange abnormalities.
double-stranded breaks; dose-dependent linear; S phase- dependent; sister chromatid exchanges
Chromosomal breakage is not randomly distributed, and for all translocations the spontaneous mutation rate is _____.
1 in 1000 gametes
Most structural chromosome aberrations in both somatic and germ cells arise from errors of _____.
recombination
Synapsis between homologous regions on non-homologous chromosomes can lead to accidental recombination between non-homologous chromosomes, resulting in _____.
chromosome rearrangements
Recombination is preceded by____ of homologous chromosomes, which involves the recognition by one homologue of complementary sequences in the other homologue.
synapsis
During synapsis, _____ can occur, particularly in regions of repetitive DNA, followed by _____, leading to duplication or deletion.
Mismatching; unequal crossing over
Sites of non-allelic homologous recombination are characterised by _____.
low copy number region-specific repeats
Rearrangement breakpoints tend to occur within segmental duplications, retrotransposons, copy number variants and other duplications with up to _____ homology.
97%
Rearrangement breakpoints via NAHR tend to be located at ____ and _____ chromosomal regions and may be in direct or inverted orientation with respect to one another.
pericentromeric; subtelomeric
Other less frequent mechanisms for constitutional chromosome aberration aside from NAHR.
non-homologous end joining; centromere repositioning
Most frequent constitutional chromosome aberrations (by chromosomal rearrangement) can be traced to _____.
NAHR
