The consequences of exposure of hydrophobic areas of polypeptide chains or their partial degradation products in the aqueous cell environment, wherein they coalesce and eventually precipitate within a cell. Aggregates are commonly found in human neurodegenerative diseases.
Proteins that activate transcription, usually by binding to specific DNA sequences in a gene promoter.
The subdivision of anaphase that involves the initial poleward movement of chromosomes on the spindle.
The splicing of different combinations of exons of a pre-mRNA that can result in the synthesis of different polypeptides or mRNAs with different stabilities. Also called differential splicing.
The subdivision of anaphase during which the spindle poles separate further apart, moving towards the cell cortex.
Anaphase promoting complex
Also known as APC. 4A complex of proteins whose activation triggers the transition from metaphase to anaphase. Activated APC both stimulates the ubiquitination of cyclins and the release of the inhibition on securin.
The phase of mitosis when sister chromatids separate from each other and migrate towards the poles of the spindle.
A deviation from the normal copy number of chromosomes within a cell, resulting from an unequal segregation of chromosomes between the daughter cells before cell division (e.g. one chromosome too few or too many).
Enzymes that are responsible for tRNA charging, i.e. the joining of the appropriate tRNA molecule to its corresponding amino acid. There is one such enzyme for each of the 20 amino acids incorporated into proteins.
Autonomously replicating sequence elements - short DNA segments that confer the ability to replicate upon small circular plasmid DNAs (serving as replication origins) in yeast cells.
These microtubules radiate from the microtubule organizing centre (MTOC) toward the cell cortex. The action of motor proteins on astral microtubules plays an important role in the movement of the spindle poles in anaphase B.
A regulatory mechanism found in some prokaryotic operons that utilizes the availability of an amino acid for translation to regulate its own biosynthetic pathways.
Base excision repair
The process of scanning and removal of single damaged bases or nucleotides, particularly depurinated or deaminated bases. The bases are removed by a family of enzymes called DNA glycolyases.
A microscopically visible body formed by the highly condensed, transcriptionally inactivated X chromosome in the cells of female mammals.
The simple division of a cell into two daughter cells following genome replication in prokaryotes.
A region within the prokaryotic gene promoter that is important for promoter activity and RNA polymerase complex assembly.
The migration of a strand exchange event between two duplex DNA chains along the paired DNA chains. This allows a site of recombination to move along paired chromosomes in meiosis.
A lectin protein that is attached to the lumenal face of the ER membrane. It plays a role in protein folding pathways by assisting with the retention of immature proteins (not fully folded) which carry glucose units on the ends of their glycosyl chains.
A nucleotide linked to the 5′ end of eukaryotic mRNAs, which influences translational efficiency and protects against mRNA degradation. The formation of the 5′ cap is the first modification to be made following transcription. It is the addition of a 7-methylguanosine residue (m7G) via three phosphate groups to the 5′ terminus of the pre-mRNA (the primary mRNA transcript) in an unusual 5′ to 5′ linkage. It is therefore also called the m7G cap.
A core consensus sequence forming part of a eukaryotic gene promoter, which plays a role in RNA polymerase assembly.
A cellular structure consisting of two small cylindrical structures composed of tubulin, oriented at right angles to each other. Centrioles are components of the centrosome, the organelle responsible for nucleating microtubule production during cell division.
The microtubule organizing centre (MTOC) found in animal cells, which is involved in assembly and maintenance of microtubules.
A cloud of diffuse material surrounding the centrioles. It is within this matrix that the microtubules of the spindle appear to nucleate.
The series of checks that a cell performs as it progresses through the cell cycle. If the checkpoints are not satisfied, the cell is inhibited from progressing further.
Class I major histocompatibility complex
Also known as MHC. Proteins that are responsible for the transport of a sample of short peptides derived by proteasome degradation of misfolded or recycled proteins, from within the cell to the cell surface. Here, these peptides are displayed to passing cells of the immune system. This allows the entire internal contents of cells to be screened to allow for the detection of any foreign antigens, which are indicative of infection.
The process in which chromosomes associate with the spindle microtubules and are moved to the spindle equator.
A generalized nucleotide sequence derived from comparisons of closely related DNA sequences from many places within or between genomes.
A structure composed of actin filaments, myosin II filaments and other structural and regulatory proteins that forms beneath the cell surface and brings about cytokinesis.
Proteins that facilitate the condensation of new replicated genomic DNA into visible chromosomes.
The antiparallel structure of DNA, combined with the requirement for synthesis to be in the 5′ to 3′ direction, means that DNA polymerase in the moving replication fork has to synthesize DNA on one strand in the direction opposite to its progress along a chromosome. To get around this problem, two DNA polymerases are combined at the replication fork and the synthesis of each strand is coordinated, both polymerases progressing in the same direction at the replication fork.
Also called recombinational repair, this is the process wherein a region of DNA is repaired by synthesis, utilizing a strand of another duplex DNA as a template. This can occur immediately after replication, with the sister chromatid or, in the absence of replication, from the homologous chromosome.
The term used to describe the folding of the newly synthesized polypeptide chain as it is being synthesized on the ribosome, i.e. as it emerges from the tunnel on the ribosome.
The term used to describe the first stage in the localization of a newly synthesized polypeptide to cellular subcompartments or for export from the cell. Proteins destined for certain compartments are actively synthesized across the ER membrane and are processed for downstream destinations.
Proteins that regulate the activity of cyclin-dependant kinases through binding with the Cdk to form a cyclin-Cdk complex. Cyclin levels increase and decrease as the cell cycle proceeds.
cyclin kinase inhibitors
Also known as CKIs. Proteins that inhibit cyclin-Cdk complex activity. This is achieved through direct binding, thus preventing the formation of the active complex.
The complex that is formed when a cyclin binds to its partner cyclin-dependent kinase (Cdk). The activity of the complex regulates progression through the cell cycle by activating or inhibiting other proteins. The complex is active in the dephosphorylated form.
Also known as Cdks. A family of phosphorylating enzymes that regulate progress of the cell cycle.
The division of the cytoplasm following nuclear division, which produces two daughter cells.
The splicing of different combinations of exons of a pre-mRNA that can result in synthesis of different polypeptides or mRNAs with different stabilities. Also called alternative splicing.
An enzyme whose function is to 'unwind' the DNA helix. Helicase activity is required for genomic DNA synthesis, during recombination and during transcription in eukaryotes.
The group of enzymes that synthesize new DNA strands on existing template DNA strands. They operate in the 5′ to 3′ direction, require a free 3′-OH and control the fidelity of nucleotide insertion through base-pairing specificity and the ability of the polymerase active site to detect mispaired bases.
The enzyme whose function is to synthesize the short primer RNA chain that will provide the necessary 3′-OH from which replicative synthesis by DNA polymerases will commence.
A family of microtubule-binding motor proteins that bind to and move towards the minus end of a microtubule. Dynein proteins will tend to bring microtubules to a focus, with their minus ends in together. Dyneins are one of the two families of motor proteins that move vesicles along microtubules.
Also known as EF. The term used to describe the ancillary protein that assists with the elongation phase of translation through binding to a charged tRNA. The elongation factor responds to the appropriate pairing of the tRNA anticodon with the mRNA codon by releasing the tRNA-amino acid into the ribosome peptide linkage site.
DNA sequences that elevate transcription rate in a position- and orientation independent manner. Enhancers are often active only in specific cell types, and at specific developmental stages.
The term applied to describe modifications to chromatin or DNA that are inherited as cells divide. These include core histone modifications and DNA methylation.
A complex of proteins that degrades RNA molecules exonucleolytically in the 3′ to 5′ direction.
The term used to describe replication of DNA elements (usually plasmid DNAs or viruses) that occurs outside the chromosomal DNA of an organism.
A mutation that causes a shift in the three-base, non-overlapping, reading frame of an ORF. This generally occurs through the insertion or deletion of either one or two nucleotides.
halt signal sequence
A short section of a polypeptide chain that signals for a halt in the transfer of the growing chain across the ER membrane, by directing detachment of the ribosome from the ER surface.
Also known as HLH. A protein motif found in many transcription factors, composed of a loop of unstructured chain interspersed between two α helices. The loop allows two proteins to interact with each other, a common formation during transcription factor dimerization.
The state of a DNA duplex when one of the two strands carries bases that have been modified, whereas the other strand does not. Such a situation arises immediately after DNA replication; hemi-methylated DNA serves to direct methylation of the other strand.
Late replicating parts of the genome, largely containing highly repetitive DNA, and few genes. Heterochromatin has a more highly compacted chromatin structure.
The arrangement of the four DNA strands after strand invasion, but before the recombination event has been resolved by strand cleavage. Holliday structures can migrate along paired duplexes by branch migration.
A class of genes that, when mutated, cause a transformation of one body part to another, homologous, part.
The term used to describe the process of strand exchange that occurs between sequences of identical (or near identical) DNA sequence. As a technique, the term is used to describe the targeted alteration to a DNA sequence through the insertion or deletion of a fragment of DNA.
A component of the pathway by which proteins are imported into the nucleus. Importin A recognizes a nuclear localization polypeptide sequence and binds to the protein. Import occurs through interaction with importin B and the Ran protein.
A component of the pathway by which proteins are imported into the nucleus. A complex of importin B and the Ran protein (carrying GTP) recognizes and binds to proteins bound to importin A and effects nuclear import.
initiator tRNA (tRNAi)
Also known as tRNAi. A specific tRNA molecule used only for the initiation of translation.
Initiator tRNAs in prokaryotes carry the modified amino acid formylmethionine, whereas in eukaryotes they carry methionine. The initiator
tRNAs interact with a specific initiation factor before binding to the ribosome.
A DNA sequence that, when located between an enhancer and a gene promoter, prevents the enhancer from influencing transcription from that promoter.
internal ribosome entry site
Also known as IRES. This is a site within a eukaryotic mRNA that lies further from the normal ATG translation initiation site at which translation initiation can occur. IRESinitiated translation will generate a truncated protein relative to that synthesized from the fulllength mRNA.
The state of the cell prior to cell division. Interphase includes the G1, S and G2 phases of the cell cycle.
The microtubules that extend from each microtubule organizing centre (MTOC) inwards towards the equator of the cell, overlapping with microtubules originating at the opposite MTOC.
A family of microtubule-binding motor proteins that bind to and move toward the plus end of a microtubule. One of the two families of motor proteins that move vesicles along microtubules.
Microtubules that extend from the microtubule organizing centre (MTOC) to the kinetochore.
A disc-shaped structure that is attached to the centromere and is the point at which the chromosome is attached to the mitotic spindle.
A term that is commonly used to describe the insertion of a segment of DNA into a target (usually chromosomal) gene by homologous recombination. It generally refers to modifications made to genes that leave them functional, but modified in some way.
A term that is commonly used to describe the process whereby a segment of a chromosomal gene is destroyed, removing the function of the gene from the cell. This is commonly achieved by targeting segments of DNA that block transcription or translation, or by deleting a segment of the target gene.
A short sequence of ribonucleotides within a eukaryotic mRNA chain, lying upstream from the ATG initiation codon, which assists with translation by directing initiation at the ATG site by the scanning initiation complex.
The strand of DNA that is replicated in small segments and lags behind replication on the leading strand.
The strand of a duplex DNA chain that is replicated continuously by a DNA polymerase during replication.
The general term used to describe a class of adhesion molecules that bind glycosyl (i.e. carbohydrate) chains (and therefore the proteins they are attached to). Calreticulin is an example of a lectin.
M phase promoting factor
Also known as MPF. The original name for cyclin B-dependent kinase (cyclin B- Cdk1). Cyclin B-Cdk1 activity controls entry in mitosis.
A 7-methylguanosine residue (m⁷G) linked via three phosphate groups to the 5′ terminus of the pre-mRNA (the primary mRNA transcript), which influences translational efficiency and protects against mRNA degradation. Also called simply the 5′ cap.
The phase of mitosis when the condensed chromosomes are aligned at the equator of the mitotic spindle.
microtubule organizing centre
Also known as the MTOC. The organelle in the cell that nucleates (i.e. initiates) the formation of microtubules. In animal cells this is called the centrosome, whilst in yeast it is called the spindle pole body (SPB).
The process by which bases within a duplex DNA chain that are mispaired (i.e. not paired A-T or G-C) are removed and repaired. This involves a family of mismatch repair proteins which detect and target the mispair for replacement by resynthesis.
The disruption of progress of the cell cycle brought about by a chemical treatment or as a result of a checkpoint.
The microtubule complex appearing during mitosis and meiosis in most eukaryotic cells. The microtubules extend from two centrosomes at opposite poles of the dividing cell. The minus ends of the microtubules are stabilized by association with the centrosome, the plus ends projecting from opposite poles overlap in the centre of the cell and are cross-linked by microtubuleassociated proteins, thereby stabilizing them and preventing depolymerization. This structure is critical to the separation of the chromatids during mitosis and meiosis.
Also known as NMD. A translation associated pathway which recognizes the presence of aberrant or premature stop codons within an ORF of a eukaryotic mRNA. It targets such mRNAs for degradation.
The process whereby eukaryotic mRNAs with no stop codons are degraded in the cell. The stalled mRNA-ribosome complex is recognized and the mRNA targeted for degradation.
Also known as NE. A highly complex structure that surrounds the nucleus, consisting of a double membrane and a protein scaffold, or nuclear lamina.
nuclear export signal
Also known as NES. A short stretch of amino acid residues within a polypeptide that directs its export, via a shuttling protein, from the nucleus.
The structural proteins that comprise the nuclear lamina. During NEBD, the nuclear lamina breaks down and the lamins become dispersed within the cytosol, some remaining associated with membrane components.
A component of the nuclear envelope found beneath the double membrane and consisting of a network of structural proteins called lamins.
nuclear localization signal
Also known as NLS. A short sequence of amino acid residues within the Nterminal region of a polypeptide chain that is recognized by importin A and targets the polypeptide for transport into the nucleus.
nuclear pore complexes
Also known as NPCs. The pore complexes in the nuclear membrane that regulates the movement of macromolecules to or from the nucleoplasm, including transcription factors, RNA molecules such as mRNA and tRNA, chromatin proteins and components of the replication, repair and transcription machinery.
nucleotide excision repair
Also known as NER. DNA damage that distorts the helix structure is detected by NER proteins, which trigger the recruitment of two endonucleases that remove a portion of the affected DNA strand.
The small nucleic acid chains that are formed during replicative DNA synthesis on the lagging strand template. As part of coordinated synthesis, Okazaki fragments are synthesized from short RNA primers which are extended by DNA polymerase. These fragments are subsequently processed to remove the RNA and ligated to form the completed lagging strand.
open reading frame (
Also known as ORF. A nucleic acid sequence with an uninterrupted series of codons, terminating with a stop codon, which encodes a polypeptide.
Sequence within a prokaryotic gene or operon promoter to which regulatory proteins bind to influence the rate of transcription.
A group of adjacent prokaryote genes whose transcription is coordinately regulated by an operator element within their common promoter.
origin recognition complex
Also known as ORC. A complex of proteins that recognizes and binds to the origins of replication in the genome and initiates replication.
origins of replication
Sites in the genome where replication is initiated by the binding of an origin recognition complex.
persistent chromatin remodelling
Changes to chromatin structure through modification of its component histones, which persist through subsequent rounds of DNA replication and cell division.
The site at which the cell wall forms in cytokinesis in plant cells. Vacuoles carrying cargoes of cell wall and membrane components accumulate at the spindle equator and fuse to form the new cell wall.
polyadenylation signal sequence
The sequence of nucleotides within an mRNA that specifies where the poly(A) tail is added.
Structures formed when multiple ribosomes are translating a single mRNA. Polysomes are enhanced through the circularization of mRNA via 5′ cap and poly(A) interactions.
Also known as PEV. The reduction in levels of expression of a gene as a consequence of a chromosome rearrangement that moves it into or close to heterochromatin, wherein the influence of the compacted, transcriptionally inert chromatin spreads to the gene.
The primary transcript before introns are removed by splicing, and before 5′ capping and 3′ poly(A) tailing.
A band of microtubules and actin filaments which assembles at the position that eventually become the site of the post-mitotic cell cleavage.
A complex of proteins bound to an origin of replication during the G1 phase of the cell cycle. Its major component is the origin recognition complex. Origins bound by the pre-replication complex will be active origins in the subsequent S phase.
Sequence of nucleotides lying approximately 10 bases 5′ of the transcription start site within a prokaryotic gene promoter to which RNA polymerase binds.
The phase of mitosis when the newly replicated chromosomes begin to condense within the intact nuclear envelope.
A large multisubunit protease. A component of the ubiquitin-mediated pathway for protein degradation. The proteosome is a closed barrel structure into which proteins are placed for degradation. The process yields short peptide chains which are further degraded by cellular proteases.
protein truncation assay
A laboratory technique used to detect stop codons within ORFs. This assay couples the in vitro transcription of an ORF to an in vitro translation reaction, the presence of a premature stop codon being detected as a truncated polypeptide chain.
A copy of a gene that no longer has the capacity to be expressed as a polypeptide. Pseudogenes commonly arise by gene duplication.
A technique in which cells undergoing DNA synthesis (usually synthesis associated with S-phase replication) are briefly exposed to a nucleotide that is labelled with some form of a molecular tracer. After synthesis is completed, the DNA that has incorporated the tracer can be visualized or isolated, allowing the direct analysis of active sites of DNA synthesis to be studied.
. A PCR-based technique in which the amount of amplified gene product directly reflects the amount of template present in the initial sample. Often used to estimate and compare levels of specific mRNA molecules.
Also known as retinoblastoma protein. In its active state, Rb inhibits cell proliferation through the inactivation of transcription factors required for the expression of the genes encoding cyclins A and E, and by generally inhibiting protein synthesis. The cyclin D-Cdk complex inactivates Rb by phosphorylation.
The process whereby two DNA duplexes interact to form the four-strand Holliday structure. Resolution of this structure allows the exchange of DNA between the two duplexes. In the case of meiosis, recombination is the process whereby two chromosomes exchange genetic information.
Also called copy repair, this is the process wherein a region of DNA is repaired by synthesis, utilizing a strand of another duplex DNA as a template. This can occur immediately after replication, with the sister chromatid or, in the absence of replication, from the homologous chromosome.
Points along the chromosome where DNA replication is initiated. These are well defined in prokaryotes and lower eukaryotes and contain A-T-rich elements.
Proteins that repress transcription, usually by binding to specific DNA sequences in a gene promoter.
The G1 checkpoint in mammals that checks that conditions are favourable for the cell to commit itself to proceeding into S phase.
Naturally occurring DNA segments that are capable of copying themselves through the action of reverse transcriptase on an RNA copy of their sequence. This DNA copy can then insert back into chromosomal DNA. This is a common mechanism of transfer exploited by viruses and other DNA elements such as transposons.
Enzymes belonging to the polymerase family. They catalyse the synthesis of DNA on an RNA template.
RNA transcription termination that requires a specific termination factor, the Rho protein.
RNA transcription termination that depends only on the sequence of bases within the mRNA.
Also known as RNAi. A technique in which small double-stranded RNA molecules are introduced into a cell, targeting mRNAs with complementary sequences for destruction. This technique uses a naturally occurring pathway for regulation of gene expression via miRNAs, involving the RISC complex.
A term used to describe the regions of the endoplasmic reticulum with ribosomes attached and within which co-translational localization occurs.
scaffold attachment regions
Also known as SARs. Regions of chromosomal DNA that are involved in a structural interaction with the chromosome scaffold and are thereby thought to play a role in limiting enhancer activity through the prevention of DNA looping.
The process by which the eukaryotic translation initiation complex moves along the mRNA from its 5′ cap to the ATG translation start site.
The cellular pathway by which proteins are secreted from cells. It is initiated by translation of the protein across the ER membrane, from where the protein follows an export pathway to the cell surface.
A protein that inhibits the activity of separase. During anaphase, the anaphase promoting complex (APC) cleaves securin, which releases the inhibition of separase, thereby allowing it to cleave the cohesin linkage between the sister chromatids.
The enzyme that cleaves the cohesin linkage that binds sister chromatids together. During anaphase, the anaphase promoting complex (APC) cleaves securin, which releases the inhibition of separase, thereby allowing it to cleave the cohesin
Shine-Dalgarno (SD) sequence
A short sequence of ribonucleotides within a prokaryotic mRNA chain that assists in translation initiation at the ATG start site. This is achieved through base pairing with an RNA chain within the small ribosomal subunit.
DNA sequences that reduce transcription in a position- and orientationindependent manner. These are often active only in specific cell types, and at specific developmental stages.
One of the two chromatids making up a chromatid pair. Both are copies of the original chromosome.
A form of recombination that occurs at specific DNA sequences. The target DNA sequences are recognized by specific forms of the recombinase enzymes and the four-strand DNA configuration occurs only at the target site.
small nuclear RNAs
Also known as snRNAs. A class of small RNA molecules, located in the nucleus, some of which are components of the spliceosome.
The situation where homologous chromosomes remain in close association throughout interphase. Inferred genetically in Drosophila.
splice site consensus sequence
The consensus sequence found at exon-intron junctions, that is important for base-pairing interactions with RNA components of the spliceosome.
The G1 checkpoint in budding yeast that checks that conditions are favourable for the cell to commit itself to proceeding into S phase.
A single large cell that contains many nuclei, e.g. as found in the early Drosophila embryo.
A consensus DNA sequence found within a eukaryotic gene promoter containing the four nucleotides 5′-TATA-3′. This is bound to TATA binding protein (TBP), a component of the transcription factor TFIID.
The phase of mitosis after chromosome separation, when the chromosomes begin to decondense, the nuclear envelope begins to re-form and cytokinesis takes place.
The DNA strand within an ORF upon which the primary RNA transcript is synthesized by complementary base pairing.
Also known as TFs. Proteins that bind to actively translating ribosomes at stop codons. These proteins have one surface that specifically recognizes stop codons in the mRNA and a region that interacts with the large ribosomal subunit. The tertiary shape of termination factors mimic those of the elongation factor-tRNA complex.
A complex of transporter proteins that spans the mitochondrial membranes and through which import of proteins into the mitochondrion is achieved.
The process by which DNA damage on the coding (sense) strand of an ORF is detected and repaired. This involves the reversal of RNA polymerase and the recruitment of excision repair proteins to the region to effect repair. Targeting repair of the coding strand helps maintain the coding integrity of an organism's genome.
The process whereby, through somatic pairing, the regulatory regions of a gene upon one chromosome can influence the homologous gene on the other chromosome.
The process by which an amino acid is linked to a tRNA. This reaction is mediated by aminoacyl synthase enzymes.
γ-tubulin ring complexes
Also known as γ-TuRCs. Protein complexes within the centrosome, containing γ-tubulin, and which play a role in nucleating microtubules.
A small, highly conserved protein that is attached to proteins through the action of ubiquitin ligases and targets them for degradation in the proteasome.
The class of enzymes that catalyse the covalent addition of ubiquitin to other proteins, thereby targeting them for degradation.
The protein degradation pathway by which proteins that are to be degraded are tagged with chains of ubiquitin by ubiquitin ligases.
Also known as UTRs. Sequences at the 5′ and 3′ ends of mRNAs that do not encode part of the polypeptide.
The base mispairing that is allowed to occur during translation, between the third base in the codon (in the mRNA) and its partner within the anticodon (on the tRNA).