Comprehensive Genetics: DNA Structure, Replication, Mutation, Expression, and Cytogenetics

Comprehensive practice flashcards defining core molecular genetics, DNA replication, mutagenesis, repair pathways, protein translation, and cytogenetics vocabulary based on lecture notes and figures.

Phosphodiester Bond

A covalent bond that forms the structural backbone of nucleic acids by linking the $3'$ carbon of one nucleotide's deoxyribose sugar to the $5'$ carbon of the adjacent nucleotide via a phosphate group.

Bacterial Transformation

The process demonstrated by Frederick Griffith in which a recipient bacterium (such as rough, nonvirulent R cells) acquires genetic traits by taking up hereditary material from heat-killed virulent S cells.

Bacteriophage T2

A virus infecting Escherichia coli composed of roughly equal amounts of protein and DNA, utilized by Hershey and Chase with $^{32}\text{P}$ and $^{35}\text{S}$ labeling to demonstrate that DNA is the injected genetic material.

Chargaff's Rules

The quantitative observation that double-stranded DNA across species maintains a roughly $1:1$ ratio of adenine to thymine ($A:T \approx 1$) and guanine to cytosine ($G:C \approx 1$).

Photo 51

The famous X-ray diffraction pattern produced by Rosalind Franklin and Maurice Wilkins revealing the double-helical dimensions, symmetry, and helical repeat of DNA.

Z-DNA

A conformation of the DNA double helix that twists into a left-handed helix with an irregular zigzagging sugar-phosphate backbone, distinct from the smooth right-handed B-DNA helix.

Semiconservative Replication

The replication mechanism proved by Meselson and Stahl in which each copied double-stranded DNA molecule consists of one conserved parental strand and one newly synthesized daughter strand.

Okazaki Fragments

Short stretches of newly synthesized DNA produced discontinuously on the lagging template strand during replication, later joined together by DNA ligase.

Topoisomerase

An enzyme that relieves the positive supercoiling ahead of an advancing replication fork by breaking, unwinding, and resealing DNA phosphodiester backbones.

Chromatin

The eukaryotic nuclear complex consisting of approximately $1/3$ DNA, $1/3$ histones, and $1/3$ nonhistone proteins, along with RNA.

Nucleosome

The fundamental packaging unit of chromatin, composed of an octamer of core histones (two each of H2A, H2B, H3, and H4) wrapped twice by roughly $160\,\text{bp}$ of DNA, connected by $40\,\text{bp}$ of linker DNA associated with histone H1.

Radial Loop-Scaffold Model

A model of chromosome compaction in which nonhistone scaffold proteins bind chromatin every $60\text{--}100\,\text{kb}$ to gather $300\,\text{Å}$ fibers into loops compressed into rosettes and mitotic chromosomes.

Heterochromatin

Highly condensed, transcriptionally silent chromatin that stains darkly, occurring either as constitutive (condensed in all cells) or facultative (condensed selectively).

Position-Effect Variegation (PEV)

A mosaic gene expression pattern resulting when a chromosomal rearrangement moves an active euchromatic gene adjacent to heterochromatin, causing spreading of transcriptional silencing.

Xist

A non-coding, cis-acting regulatory RNA transcribed specifically from the future inactive X chromosome that coats the chromosome and initiates heterochromatin formation during Barr body formation.

Telomerase

A ribonucleoprotein reverse transcriptase that extends the $3'$ ends of linear chromosomes by adding species-specific repetitive DNA sequences to solve the end-replication problem.

Shelterin

A multi-protein protective complex that binds eukaryotic telomeric repeats and folds chromosome ends to prevent degradation by nucleases and prevent inappropriate nonhomologous end-joining.

CENP-A

A specialized histone H3 variant that replaces normal H3 in centromeric nucleosomes to serve as the structural foundation for kinetochore assembly.

Shugoshin

A meiosis-specific protector protein that prevents the cleavage of centromeric cohesin by separase during anaphase I, ensuring sister chromatids remain paired until anaphase II.

Spo11

A specialized meiosis-specific enzyme that initiates homologous recombination by introducing a deliberate double-strand break in both phosphodiester backbones of one chromatid.

Dmc1

A meiosis-specific recombinase protein that coats single-stranded $3'$ DNA tails created by resection to facilitate strand invasion into a non-sister chromatid.

Heteroduplex

A region of double-stranded DNA formed during recombination in which one strand is derived from the maternal chromosome and the complementary strand is derived from the paternal chromosome.

Gene Conversion

A non-reciprocal transfer of genetic information during meiotic recombination that leads to non-Mendelian segregation ratios (such as $3:1$ or $1:3$ instead of $2:2$) due to mismatch repair within a heteroduplex region.

Transition Mutation

A single-base substitution in which a purine is replaced by another purine ($\text{A} \leftrightarrow \text{G}$) or a pyrimidine is replaced by another pyrimidine ($\text{C} \leftrightarrow \text{T}$).

Transversion Mutation

A single-base substitution in which a purine is replaced by a pyrimidine or vice versa ($\text{purine} \leftrightarrow \text{pyrimidine}$).

Fluctuation Test

An experimental assay designed by Salvador Luria and Max Delbrück showing that bactericide resistance in bacteria arises from random mutations occurring prior to antibiotic exposure rather than physiological adaptation.

Depurination

A spontaneous DNA lesion occurring roughly $1000$ times per hour per mammalian cell in which a glycosidic bond hydrolyzes, releasing an adenine or guanine and leaving an apurinic (AP) site.

8-oxodG (GO)

A damaged guanine base altered by active oxygen species that mispairs with adenine during DNA replication, resulting in a $\text{G:C} \rightarrow \text{T:A}$ transversion mutation.

5-Bromouracil (5BU)

A thymine base analog whose rare enol tautomer resembles cytosine, pairing with guanine and causing $\text{T:A} \leftrightarrow \text{C:G}$ transition mutations across rounds of replication.

Ames Test

An experimental screening assay that evaluates the mutagenicity and carcinogenicity of chemical compounds by measuring the frequency of revertants from $\text{His}^-$ to $\text{His}^+$ in Salmonella in the presence of rat liver enzymes.

Base Excision Repair (BER)

An accurate repair pathway where a DNA glycosylase excises an altered base to create an AP site, followed by AP endonuclease cutting, nick translation/excision by DNA polymerase, and ligation.

Methyl-Directed Mismatch Repair

A bacterial post-replication repair mechanism where MutS and MutL bind a mismatch, recruiting MutH to introduce a nick in the unmethylated nascent strand opposite a hemimethylated GATC sequence.

Complementation Group

A collection of recessive mutations that fail to restore the wild-type phenotype when paired in trans, indicating that the mutations affect the same functional gene.

Auxotroph

A mutant nutritional strain that has lost the ability to synthesize an essential metabolite and can only grow when supplemented with that specific nutrient in minimal medium.

Pleiotropy

A genetic condition in which a single gene mutation results in multiple distinct phenotypic abnormalities, such as the single amino acid substitution in sickle-cell anemia causing anemia, spleen damage, and kidney failure.

Sigma (\sigma) Factor

A bacterial transcription initiation factor that binds RNA polymerase core enzyme, enabling it to recognize and bind specific promoter consensus elements at $-35$ and $-10$.

Intrinsic Terminator

A transcription termination sequence in prokaryotes that forms a hairpin loop structure followed by a run of uracils in the nascent transcript, causing RNA polymerase release without rho (\rho) factor.

5' Methylated Cap

A post-transcriptional modification added to the $5'$ end of eukaryotic pre-mRNAs consisting of a 7-methylguanosine residue connected via a backward $5'\text{-to-}5'$ triphosphate bridge.

Lariat Intermediate

A transient branched circular-loop structure formed during pre-mRNA splicing when the $5'$ splice donor site (GU) links covalently via a $2'\text{-to-}5'$ phosphodiester bond to an internal adenosine at the branch site.

Aminoacyl-tRNA Synthetase

An enzyme that attaches a specific amino acid to the $3'$ CCA terminus of its cognate tRNA through an energy-dependent charging reaction.

Wobble Position

Flexibility in base pairing between the $5'$ base of a tRNA anticodon and the $3'$ base of an mRNA codon, allowing a single tRNA species to decode multiple degenerate codons.

Shine-Dalgarno Box

A conserved purine-rich sequence ($5'\text{-AGGAGG-}3'$) located upstream of the AUG start codon in prokaryotic mRNA that pairs with the $16\text{S}$ rRNA to direct translation initiation.

Peptidyl Transferase

The ribozyme catalytic center residing within the large ribosomal subunit ($23\text{S}$ rRNA in prokaryotes; $28\text{S}$ rRNA in eukaryotes) that forms covalent peptide bonds between amino acids.

Haploinsufficiency

A condition in a diploid organism where having only a single functional wild-type allele produces insufficient protein product ($50\%$ normal dosage) to yield a normal phenotype, producing a dominant mutant phenotype (such as GLI3-induced polydactyly).

Neomorphic Mutation

A dominant gain-of-function mutation causing a gene product to acquire an entirely new activity or to be expressed ectopically in an abnormal tissue location or developmental time.

Antimorphic Allele

A dominant-negative mutant allele whose defective protein product poisons or disrupts the assembly and function of normal wild-type protein subunits within a multimeric complex.

Nonsense Suppressor tRNA

A mutant tRNA containing an altered anticodon that base-pairs with a premature stop codon, inserting an amino acid and allowing completion of full-length protein translation.

Pericentric Inversion

A chromosomal rearrangement resulting from two breaks that span both chromosomal arms, producing a $180^\circ$ rotation of a segment that includes the centromere.

Paracentric Inversion

A chromosomal inversion restricted to a single chromosome arm that does not encompass the centromere.

Balancer Chromosome

A specially engineered chromosome containing multiple inversions, a dominant phenotypic marker, and a recessive lethal mutation, used in genetic crosses to suppress viable recombination.

Reciprocal Translocation

A balanced chromosomal rearrangement caused by breakage and two-way exchange of chromosome segments between two non-homologous chromosomes.

Semisterility

A condition seen in reciprocal translocation heterozygotes characterized by roughly $50\%$ reproductive viability, caused by inviable gametes produced through adjacent-1 and adjacent-2 segregations.

Robertsonian Translocation

A chromosomal rearrangement in which two acrocentric chromosomes break near their centromeres and their long arms fuse to form a single large metacentric chromosome with loss of the tiny short-arm heterochromatin fragments.

Retrotransposon

A transposable genetic element that mobilizes through a 'copy-and-paste' mechanism by transcribing into an RNA intermediate and reverse-transcribing into double-stranded DNA before integrating into a new genomic locus.

Autonomous Transposable Element

A mobile genetic element (such as the maize Ac element) that encodes its own functional transposase and contains intact inverted repeats, allowing it to move independently.

Antisense Strand

The template DNA strand oriented in the $3' \rightarrow 5'$ direction that is complementary to mRNA and serves as the template read by RNA polymerase during transcription.

Sense Strand

The non-template coding strand of DNA oriented in the $5' \rightarrow 3'$ direction whose sequence corresponds directly to the mRNA transcript, with thymine instead of uracil.