In
molecular biology
Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...
, a displacement loop or D-loop is a
DNA structure where the two strands of a double-stranded DNA molecule are separated for a stretch and held apart by a third strand of DNA. An
R-loop
An R-loop is a three-stranded nucleic acid structure, composed of a DNA: RNA hybrid and the associated non-template single-stranded DNA. R-loops may be formed in a variety of circumstances, and may be tolerated or cleared by cellular components. ...
is similar to a D-loop, but in this case the third strand is RNA rather than DNA. The third strand has a
base sequence which is
complementary
A complement is something that completes something else.
Complement may refer specifically to:
The arts
* Complement (music), an interval that, when added to another, spans an octave
** Aggregate complementation, the separation of pitch-class ...
to one of the main strands and
pairs
Concentration, also known as Memory, Shinkei-suijaku (Japanese meaning "nervous breakdown"), Matching Pairs, Match Match, Match Up, Pelmanism, Pexeso or simply Pairs, is a card game in which all of the cards are laid face down on a surface and tw ...
with it, thus displacing the other complementary main strand in the region. Within that region the structure is thus a form of
triple-stranded DNA
Triple-stranded DNA (also known as H-DNA or Triplex-DNA) is a DNA structure in which three oligonucleotides wind around each other and form a triple helix. In triple-stranded DNA, the third strand binds to a B-form DNA (via Watson–Crick bas ...
. A diagram in the paper introducing the term illustrated the D-loop with a shape resembling a capital "D", where the displaced strand formed the loop of the "D".
D-loops occur in a number of particular situations, including in
DNA repair
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA dam ...
, in
telomere
A telomere (; ) is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes. Although there are different architectures, telomeres, in a broad sense, are a widespread genetic feature mos ...
s, and as a semi-stable structure in
mitochondrial
A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is use ...
circular DNA molecules.
In mitochondria
Researchers at
Caltech
The California Institute of Technology (branded as Caltech or CIT)The university itself only spells its short form as "Caltech"; the institution considers other spellings such a"Cal Tech" and "CalTech" incorrect. The institute is also occasional ...
discovered in 1971 that the circular mitochondrial DNA from growing cells included a short segment of three strands which they called a displacement loop.
[
They found the third strand was a replicated segment of the heavy strand (or H-strand) of the molecule, which it displaced, and was ]hydrogen bond
In chemistry, a hydrogen bond (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing a ...
ed to the light strand (or L-strand). Since then, it has been shown that the third strand is the initial segment generated by a replication of the heavy strand that has been arrested shortly after initiation and is often maintained for some period in that state.
The D-loop occurs in the main non-coding area of the mitochondrial DNA molecule, a segment called the control region or D-loop region.
Replication of the mitochondrial DNA can occur in two different ways, both starting in the D-loop region.
One way continues replication of the heavy strand through a substantial part (e.g. two-thirds) of the circular molecule, and then replication of the light strand begins. The more recently reported mode starts at a different origin within the D-loop region and uses coupled-strand replication with simultaneous synthesis of both strands.
Certain bases within the D-loop region are conserved, but large parts are highly variable and the region has proven to be useful for the study of the evolutionary history of vertebrates.
The region contains promoters for the transcription
Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including:
Genetics
* Transcription (biology), the copying of DNA into RNA, the fir ...
of RNA
Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
from the two strands of mitochondrial DNA immediately adjacent to the D-loop structure that is associated with initiation of DNA replication. D-loop sequences are also of interest in the study of cancers.
The function of the D-loop is not yet clear, but recent research suggests that it participates in the organization of the mitochondrial nucleoid
The nucleoid (meaning ''nucleus-like'') is an irregularly shaped region within the prokaryotic cell that contains all or most of the genetic material. The chromosome of a prokaryote is circular, and its length is very large compared to the cell dim ...
.
In telomeres
In 1999 it was reported that telomere
A telomere (; ) is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes. Although there are different architectures, telomeres, in a broad sense, are a widespread genetic feature mos ...
s, which cap the end of chromosome
A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...
s, terminate in a lariat
A lasso ( or ), also called lariat, riata, or reata (all from Castilian, la reata 're-tied rope'), is a loop of rope designed as a restraint to be thrown around a target and tightened when pulled. It is a well-known tool of the Spanish an ...
-like structure termed a T-loop (Telomere-loop).
This is a loop of both strands of the chromosome which are joined to an earlier point in the double-stranded DNA by the 3' strand end invading the strand pair to form a D-loop. The joint is stabilized by the shelterin
Shelterin (also called telosome) is a protein complex known to protect telomeres in many eukaryotes from DNA repair mechanisms, as well as to regulate telomerase activity. In mammals and other vertebrates, telomeric DNA consists of repeating double ...
protein POT1
Protection of telomeres protein 1 is a protein that in humans is encoded by the ''POT1'' gene.
Function
This gene is a member of the telombin family and encodes a nuclear protein involved in telomere maintenance. Specifically, this protein func ...
. The T-loop, which is completed by the D-loop splice, protects the end of the chromosome from damage.
In DNA repair
When a double-stranded DNA molecule has suffered a break in both strands, one repair mechanism available in diploid
Ploidy () is the number of complete sets of chromosomes in a cell, and hence the number of possible alleles for autosomal and pseudoautosomal genes. Sets of chromosomes refer to the number of maternal and paternal chromosome copies, respectively ...
eukaryotic
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
cells is homologous recombination repair
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 ...
. This makes use of the intact chromosome homologous to the broken one as a template to bring the two double-stranded pieces into correct alignment for rejoining. Early in this process, one strand of one piece is matched to a strand of the intact chromosome and that strand is used to form a D-loop at that point, displacing the intact chromosome's other strand. Various ligation and synthesis steps follow to effect the rejoining.
In humans, the protein RAD51
DNA repair protein RAD51 homolog 1 is a protein encoded by the gene ''RAD51''. The enzyme encoded by this gene is a member of the RAD51 protein family which assists in repair of DNA double strand breaks. RAD51 family members are homologous to th ...
is central to the homologous search and formation of the D-loop. In the bacterium
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
''Escherichia coli
''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...
'', a similar function is performed by the protein RecA
RecA is a 38 kilodalton protein essential for the repair and maintenance of DNA. A RecA structural and functional homolog has been found in every species in which one has been seriously sought and serves as an archetype for this class of homolog ...
.
Meiotic recombination
During meiosis
Meiosis (; , since it is a reductional division) is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately resu ...
, repair of double-strand damages, particularly double-strand breaks, occurs by the recombination process outlined in the accompanying diagram. As shown in the diagram, a D-loop plays a central role in meiotic recombinational repair of such damages. During this process, Rad51
DNA repair protein RAD51 homolog 1 is a protein encoded by the gene ''RAD51''. The enzyme encoded by this gene is a member of the RAD51 protein family which assists in repair of DNA double strand breaks. RAD51 family members are homologous to th ...
and Dmc1
Meiotic recombination protein DMC1/LIM15 homolog is a protein that in humans is encoded by the ''DMC1'' gene.
Meiotic recombination protein Dmc1 is a homolog of the bacterial strand exchange protein RecA. Dmc1 plays the central role in homologous ...
recombinases bind the 3’ single-strand DNA (ssDNA) tails to form helical nucleoprotein
Nucleoproteins are proteins conjugated with nucleic acids (either DNA or RNA). Typical nucleoproteins include ribosomes, nucleosomes and viral nucleocapsid proteins.
Structures
Nucleoproteins tend to be positively charged, facilitating int ...
filaments that perform a search for intact homologous double-stranded DNA (dsDNA). Once the homologous sequence is found, the recombinases facilitate invasion of the ssDNA end into the homologous dsDNA to form a D-loop. After strand exchange, 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 ...
intermediates are processed by either of two distinct pathways (see diagram) to form the final recombinant chromosomes.
See also
* D-loop replication
* mtDNA control region
The mtDNA control region is an area of the mitochondrial genome which is non-coding DNA. This region controls RNA and DNA synthesis. It is the most polymorphic region of the human mtDNA genome, with polymorphism concentrated in hypervariab ...
References
{{Reflist, 2
DNA
Telomeres