Question

How might defective double- strand break repair lead to gross chromosomal rearrangement?

Answer 1

All organisms go through double-strand breaks (DSBs) in their DNA as a result of various factors, for example exposure to ionizing radiation. These can also be formed when DNA lesions or repair intermediate encounters replication fork. During the processing and repairing of DSBs- various things take place which can cause cell death or cancer these things are mutation, loss of heterozygosity, and chromosomal rearrangement etc.

Complete solution:
Double-strand breaks (DSBs) in DNA form as a result of exposure to exogenous agents such as radiation and certain chemicals, as well as through endogenous processes, including DNA replication and repair.
The etiology of DSBs i.e. whether they are formed from high or low radiations defines the manner in which they are repaired.
A chromosomal rearrangement is a mutation that is a type of chromosome abnormality in which there is a change in the structure of the native chromosome. Such types of changes may involve various different classes of events, like deletions, duplications, inversions, and translocations.
DNA double strand breaks (DSBs) appear on a regular basis in the genome of human cells. If left unrepaired these lesions can lead to cell death, therefore the repairing of these broken chromosomes is very essential, and this repairment is either homology dependent or by non homologous mechanism.
Chromosomal translocations are induced by double strand breaks (DSBs) in DNA, these translocations are a major cause of cancer and the mechanism of these chromosomal translocations is still unknown.

Note:
DNA double strand breaks (DSBs) are the most cytotoxic lesions because they can lead to cell death or result in genome mutagenesis and chromosomal translocations. Generally most of these rearrangements have detrimental effects for cellular survival but sometimes single events can provide clonal advantage and result in abnormal cellular proliferation and cancer. The key factors at which the frequency of these events appear depends on the origin and the environment of the DNA break or the repair pathway.