DNA double-strand breaks are repaired by means of two main mechanisms: nonhomologous end joining and homologous recombination
(see Figure 1). Both mechanisms operate in all eukaryotic cells that have been examined but the relative contribution of each mechanism varies.
Can homologous recombination repair broken replication forks?
Homologous recombination is also involved in the rescue of replication forks impeded in their progression and in the repair of broken forks
. In bacteria, homologous recombination contributes to reassembling a functional replisome at inactivated replication forks [5].
What type of damage does homologous recombination repair?
1.1 DNA Synthesis in Homologous Recombination
Homologous recombination (HR) faithfully repairs
complex DNA damage including DNA double-stranded breaks (DSBs)
by referencing an intact donor template in the form of the sister chromatid, a homolog, or an ectopic sequence.
What is the resolution in homologous recombination in a double strand break repair pathway?
In this pathway, a double-strand break present in one chromatid is repaired using its intact sister chromatid as a template. The repair of breaks by homologous recombination is thus a
high fidelity process
which ensures that all the genetic information at the break site is retained.
How does homologous recombination repair work?
Homologous recombination repair is a DNA repair process that includes
the invasion of an undamaged DNA molecule by a damaged molecule of identical or very similar sequence
. Resynthesis of the damaged region is accomplished using the undamaged molecule as a template.
What can cause double-strand breaks?
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
.
What is double homologous recombination?
Homologous recombination is
a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids
(usually DNA as in cellular organisms but may be also RNA in viruses).
What is Holliday model?
Holliday’s model was
one of the first that explained most of the genetic data available at the time by a mechanism m involving the breakage, reunion, and repair of DNA molecules
. Homologous recombination is an essential cellular process catalyzed by enzymes specifically made and regulated for this purpose.
How does homology directed repair work?
Homology directed repair (HDR) is
a mechanism in cells to repair double-strand DNA lesions
. The most common form of HDR is homologous recombination. The HDR mechanism can only be used by the cell when there is a homologous piece of DNA present in the nucleus, mostly in G2 and S phase of the cell cycle.
Which mechanism of DNA repair is responsible for gene conversion?
(1) The
double-strand break repair model
. A double-strand break is expanded to a gap, which is then repaired by copying a homologous sequence. The gene conversion is often accompanied by crossing-over of the flanking sequences.
How does non homologous end joining work?
Non-homologous end joining (NHEJ) is a pathway that
repairs double-strand breaks in DNA
. NHEJ is referred to as “non-homologous” because the break ends are directly ligated without the need for a homologous template, in contrast to homology directed repair, which requires a homologous sequence to guide repair.
What is DNA repair system?
DNA repair,
any of several mechanisms by which a cell maintains the integrity of its genetic code
. DNA repair ensures the survival of a species by enabling parental DNA to be inherited as faithfully as possible by offspring. It also preserves the health of an individual.
How common are double stranded breaks?
Another study estimates that, in normal human cells,
∼1% of single-strand lesions are converted to ∼50 DSBs per cell per cell cycle
, that is, about one DSB per 10
8
bp (Vilenchik and Knudson 2003).
What is the difference between homologous and nonhomologous recombination?
Two types of recombination are typically distinguished:
homologous recombination, where a fragment of a genome is replaced by the corresponding sequence from another genome
[4], and non-homologous recombination, which causes genetic additions of new material and is also called lateral gene transfer (LGT) [5].
What happens homologous recombination?
Homologous Recombination
Paired chromosomes from the male and female parent align so that similar DNA sequences from the paired chromosomes cross over each other
. Crossing over results in a shuffling of genetic material and is an important cause of the genetic variation seen among offspring.
How many double-strand breaks a day?
The best known of such lesions is the DNA double-strand break (DSB). DNA DSBs occur in any given cell in the order of
10 to 50 per cell per day
, depending on cell cycle and tissue (Vilenchik and Knudson, 2003).
What happens if homologous recombination fails?
Homologous recombination and repair of DSBs. DSBs can be frank (two-sided) and one-sided; both are a major threat to genomic stability. Failure to repair DSBs or their misrepair can result in
chromosome loss, chromosomal rearrangements, apoptosis, or carcinogenesis
76
.
Why is repairing a single-stranded break more efficient than repairing a double-stranded break?
Why is repairing a single-stranded break more efficient than repairing a double-stranded break?
It does not require another chromosome to repair
. It doesn’t result in a loss of nucleotides. You just studied 16 terms!
What is the role of recombination in repairing damaged DNA?
Recombination repair is
a mechanism for generating a functional DNA molecule from two damaged molecules
. It is an essential repair process for dividing cells because a replication fork may arrive at a damaged site, such as a thymine dimer, before the excision repair system has eliminated damage.
How are Holliday junctions broken?
Cleavage, or resolution, of the Holliday junction can occur in two ways. Cleavage of the original set of strands leads to two molecules that may show gene conversion but not chromosomal crossover, while cleavage of the other set of two strands causes the resulting recombinant molecules to show crossover.
How do Holliday junctions work?
Holliday junction, cross-shaped structure that forms during the process of genetic recombination,
when two double-stranded DNA molecules become separated into four strands in order to exchange segments of genetic information
.
What is a heteroduplex DNA?
A heteroduplex is a double-stranded (duplex) molecule of nucleic acid originated through the genetic recombination of single complementary strands derived from different sources, such as from different homologous chromosomes or even from different organisms.
