2. DNA Flashcards

Question

Helicase

Answer 1

An ATP-dependent enzyme that unwinds and separates the two DNA strands at the replication fork.

Answer 2

An enzyme that synthesizes new DNA strands in the 5'→3' direction using a DNA template; it requires an existing primer and also performs proofreading.

Answer 3

An enzyme that seals nicks in the sugar-phosphate backbone by forming phosphodiester bonds, joining Okazaki fragments on the lagging strand.

Answer 4

Short DNA segments synthesized discontinuously on the lagging strand and later joined together by DNA ligase.

Answer 5

DNA replication in eukaryotic cells is a semi-conservative and highly regulated process that occurs during the S phase of the cell cycle. Replication begins at thousands of origins of replication distributed along each linear chromosome. At each origin, the pre-replicative complex is assembled, and helicase is activated to unwind the double helix, generating two replication forks. Single-stranded DNA-binding proteins stabilize the unwound strands. Because DNA polymerases can synthesize DNA only in the 5′→3′ direction and cannot initiate synthesis de novo, primase synthesizes short RNA primers. The leading strand is synthesized continuously by DNA polymerase ε in the direction of fork progression, whereas the lagging strand is synthesized discontinuously by DNA polymerase δ, forming Okazaki fragments. RNA primers are removed by RNase H and flap endonuclease 1 (FEN1). DNA polymerase fills the resulting gaps, and DNA ligase I seals the nicks to produce continuous DNA strands. The process continues until adjacent replication forks meet. Telomerase is required to maintain the ends of linear chromosomes and prevent progressive telomere shortening.

Answer 6

**Definition** **Telomeres are repetitive DNA sequences (TTAGGG in humans) located at the ends of linear chromosomes. They are bound by a specific protein complex called shelterin, which protects chromosome ends from being recognized as DNA breaks.** **Function** 1. **Protect chromosome ends** from degradation, end-to-end fusion, and inappropriate DNA repair. 2. **Maintain genome stability** by preventing chromosomal rearrangements. 3. **Act as a “mitotic clock”**, shortening with each cell division and limiting proliferative capacity (replicative senescence) ⇒ Aging coding 4. **Allow proper completion of DNA replication**, compensating for the end-replication problem. **Mechanism** Telomeres shorten during each S phase because DNA polymerase cannot fully replicate the 3’ ends of the lagging strand. As a result, cells gradually lose telomeric DNA. When telomeres become critically short, the cell undergoes senescence or apoptosis. - 染色体の端の **TTAGGG 繰り返し配列** - **Shelterin 複合体**によって保護される - 端が壊れたり、DNA損傷と誤認されないようにする - 細胞分裂のたびに短くなる → **細胞の寿命時計（senescence の原因）**

Answer 7

**◆ 重要ポイント** - 原因：DNA polymerase の **end-replication problem** - 解決策：telomerase が TTAGGG を追加 - telomere が短くなると → **senescence → aging** **Definition** **Telomerase is a ribonucleoprotein enzyme complex that extends telomeres at specific cells. It contains a reverse transcriptase subunit (TERT) and an RNA template (TERC) that provides the sequence used to synthesize new telomeric repeats.** **Function** 1. **Elongates telomeres** to counteract telomere shortening. 2. **Maintains long-term proliferative capacity** in germ cells, stem cells, and activated lymphocytes. 3. **Prevents replicative senescence** in cells that require continuous renewal. 4. **Reactivated in most cancers**, enabling unlimited proliferation. Locaiton - germline cells - Bone marrow stem cells - gamete (reproductive cell) - 90 % of cancer cells **Mechanism** 1. Telomerase binds to the 3’ overhang of the telomere. 2. The RNA component (TERC) base-pairs with the telomeric repeat. 3. The reverse transcriptase (TERT) synthesizes additional TTAGGG repeats. 4. After extension, DNA polymerase synthesizes the complementary strand. 5. Telomeres regain length, preventing chromosomal erosion. - **TERT（タンパク） + TERC（RNA）** からなる - **逆転写酵素**として働き、テロメアを伸ばす - **幹細胞・生殖細胞・リンパ球**で活性 - **がん細胞は再活性化**して不死化に貢献

Answer 8

Code: in DNA Codon: in RNA Anticodon: in tRNA

Answer 9

- The genetic code is composed of **triplets**: one triplet encode one amino acid - The genetic code is **redundant:** many amino acids are encoded by more than one triplets - The genetic code is „**comma-free**”: the triplets are not isolated units - The genetic code is **universal**: every living being is descended from a single common ancestor

Answer 10

**English Definition** The **Open Reading Frame (ORF)** is a sequence within a gene or messenger RNA (mRNA) that begins with a translation initiation codon (such as AUG, encoding methionine) and ends with a termination (stop) codon (UAA, UAG, or UGA). The ORF defines the specific stretch of sequence that is translated into a polypeptide chain. An **ORF mutation** is a change in the nucleotide sequence of DNA or RNA that directly alters the composition or integrity of this reading frame, thereby affecting the primary structure (amino acid sequence) or the length of the resulting protein. Key types of mutations that constitute ORF mutations include: 1. **Frameshift Mutations:** These involve the insertion or deletion of one or several nucleotides (not multiples of three) within the protein-coding region. Because the genetic code is **comma-free**, inserting or deleting a base alters the reading machinery's grouping of nucleotides into triplets downstream (in the 3' direction), making the genetic message nonsensical. 2. **Nonsense Mutations:** These are point mutations that convert an amino acid-coding triplet into one of the three stop codons (TAA, TAG, TGA). This causes protein synthesis to halt prematurely, leading to a **shorter (truncated) protein**. 3. **Read-Through Mutations:** These convert a stop codon (e.g., TAA) into a codon that codes for an amino acid (e.g., GAA). The translational machinery subsequently fails to stop and continues reading non-coding regions, which produces a **longer protein** that may suffer negative functional effects. -------------------------------------------------------------------------------- **日本語のわかりやすい説明** **ORF（Open Reading Frame、オープンリーディングフレーム）** とは、mRNAの配列のうち、実際にタンパク質へと翻訳される領域のことです。具体的には、翻訳開始の合図となる**開始コドン**（メチオニンをコードするAUGなど）から、翻訳終了の合図である**終止コドン**（UAA、UAG、UGAのいずれか）まで続く、連続したコドンの並びを指します。 **ORF変異**とは、このタンパク質設計図であるORF内の塩基配列が変化し、結果として作られるタンパク質の**アミノ酸配列や長さが変わってしまう変異**の総称です。代表的なORF変異とその影響は以下の通りです。 1. **フレームシフト変異 (Frameshift Mutation):** ◦ **変異の仕組み:** 遺伝子を構成する塩基（ヌクレオチド）が、3の倍数ではない数だけ挿入または欠失することによって起こります。 ◦ **影響:** 遺伝コードは区切り（コンマ）がないため、一度読み取りの枠がずれてしまうと、**それ以降の全てのコドン（3塩基の組）の読み方が変わり**、全く意味の通らない、機能しないタンパク質ができてしまいます。 2. **ナンセンス変異 (Nonsense Mutation):** ◦ **変異の仕組み:** あるアミノ酸を指定していたコドンが、**終止コドン**に置き換わる点変異です。 ◦ **影響:** 翻訳の途中で強制的にストップがかかるため、**本来の長さよりも大幅に短い（切断された）タンパク質**が生成され、多くの場合、機能が失われます。 3. **リードスルー変異 (Read-Through Mutation):** ◦ **変異の仕組み:** 本来終止コドンであったはずのコドンが、アミノ酸をコードするコドンに置き換わってしまう変異です。 ◦ **影響:** 翻訳機構が停止信号を認識できずに、タンパク質コード領域の**後方にある非コード領域まで読み進めてしまう**ため、通常よりも**長いタンパク質**が作られてしまい、機能に異常をきたす可能性があります

Answer 11

Mutation occurring in non-reproductive (somatic) cells; not inherited but can lead to diseases such as cancer.

Answer 12

Mutation occurring in gametes (sperm or egg); heritable and transmitted to offspring.

Answer 13

Mutation affecting a single nucleotide, including substitutions, insertions, or deletions of one base pair.

Answer 14

Mutation occurring within an Open Reading Frame, potentially altering the encoded protein sequence.

Answer 15

Mutation in which one or more nucleotides or chromosomal segments are removed.

Answer 16

Addition of one or more nucleotides or DNA segments into the genome.

Answer 17

Nucleotide change that does not alter the amino acid due to redundancy of the genetic code.

Answer 18

Base substitution that changes one amino acid to another.

Answer 19

Mutation converting a codon into a stop codon, producing truncated proteins.

Answer 20

Condition in which an organism has more than two complete sets of chromosomes.

Answer 21

Presence of an abnormal number of chromosomes (e.g., 45 or 47 instead of 46).

Answer 22

Complete chromosome set of an organism, typically shown as a chromosome spread.

Answer 23

Monosomy X (45,X); affects females; short stature, infertility, streak ovaries.

Answer 24

Trisomy 21; causes developmental delay, characteristic facial features, congenital defects.

Answer 25

47,XXY; males with hypogonadism, infertility, tall stature, gynecomastia.

Answer 26

Exchange of DNA segments between homologous chromosomes during meiosis I, increasing genetic diversity.

Answer 27

Capable of causing mutations (e.g., UV light, chemicals, radiation).

Answer 28

Spontaneous structural shifts in nucleotide bases that cause mispairing during DNA replication. Definition（短く完璧） Tautomeric transformations are spontaneous chemical shifts in DNA bases, in which a base transiently converts to a rare tautomeric form, causing abnormal base-pairing during replication and leading to point mutations. Function/Effect（必ず書くと点が上がる） These shifts can result in mispairing (e.g., T–G or A–C), producing transition mutations if not corrected. 🇯🇵 一言まとめ（日本語）塩基が“一瞬だけ姿を変える” その瞬間に複製が起きると、誤った相手とくっつく → 点突然変異を起こす原因になる

Answer 29

Mutation occurring naturally without external mutagens; caused by replication errors or base instability.

Answer 30

Mutation triggered by external mutagens (chemicals, UV, X-rays).

Answer 31

Mutation that reduces or abolishes the activity of a gene product. Ressesive e.g. Amorphic hypomorphic

Answer 32

Mutation that increases gene activity or creates a new function; often dominant.

Answer 33

Failure in DNA repair pathways leading to genome instability; associated with diseases like cancer.

Answer 34

DNA polymerase 3'→5' exonuclease activity that corrects misincorporated nucleotides during replication.

Answer 35

Post-replicative system removing incorrectly paired bases not fixed by proofreading.

Answer 36

Repair mechanism after DNA replication that removes damaged bases (by environmetntal factor) or nucleotides and fills the gap with DNA polymerase I.

Answer 37

Enzyme that removes nucleotides from the end of a DNA strand. e.g. Exosome

Answer 38

Enzyme that cuts DNA internally within the strand; essential for many repair pathways.

Answer 39

**Correct: b**

Answer 40

**Correct: c**

Answer 41

Correct: b

Answer 42

Aneuploidy =Down syndrome

Answer 43

Endonuclease

Answer 44

Mispairing bases

Answer 45

Proofreading

Answer 46

Aneuploidy -Turner syndrome -Down Syndrome -Kleifen..

Answer 47

DNA mutations are heritable changes in the nucleotide sequence of the genome, and they can occur at several different structural levels. The simplest forms are **point mutations**, which affect a single nucleotide. These include *silent mutations*, which do not alter the amino acid sequence; *missense mutations*, which substitute one amino acid for another; and *nonsense mutations*, which introduce a premature stop codon and usually truncate the protein. Insertions and deletions can remove or add nucleotides; when their length is not a multiple of three, they cause a frameshift and often produce nonfunctional proteins. Larger-scale mutations include chromosomal abnormalities. **Polyploidy** involves changes in the entire set of chromosomes, while **aneuploidy** results from the gain or loss of individual chromosomes due to nondisjunction. Specific examples include **Down syndrome** (trisomy 21), **Turner syndrome** (XO), and **Klinefelter syndrome** (XXY). Mutations can also occur within open reading frames (ORFs), potentially disrupting coding sequences. Functionally, mutations can be classified as **loss-of-function** or **gain-of-function**. Loss-of-function mutations reduce or eliminate the activity of a gene product, while gain-of-function mutations create a new or enhanced activity. Mutations arise either spontaneously—often through tautomeric shifts or replication errors—or can be induced by mutagens such as radiation or chemicals. Depending on the mutation type and location, the effects can range from benign to severely detrimental.

Answer 48

Mutations arise through both **spontaneous** and **induced** mechanisms. **Spontaneous mutations** occur naturally without external influence. One major source is **tautomeric shifts**, in which nucleotides temporarily adopt alternative chemical forms that mispair during replication, leading to point mutations. Another cause is DNA polymerase errors that escape proofreading. Additionally, spontaneous depurination and deamination reactions can alter bases and create mismatches. **Induced mutations** result from exposure to **mutagens**, which increase the mutation rate. Chemical mutagens, such as base analogs or alkylating agents, modify base-pairing properties and lead to misincorporation. Intercalating agents insert themselves between base pairs, causing insertions or deletions. Physical mutagens like UV radiation create thymine dimers, while ionizing radiation induces double-strand breaks. Both forms of mutation contribute to genetic variation but can also disrupt gene function. Cells possess multiple repair pathways to counter these changes; however, if repair systems fail or are overwhelmed, permanent mutations become fixed in the genome.

Answer 49

Cells rely on several DNA repair pathways to maintain genomic stability and prevent harmful mutations. During replication, **proofreading repair** is performed by DNA polymerases, which detect and remove incorrectly paired nucleotides using their 3′→5′ exonuclease activity. Errors that escape proofreading are corrected after replication by the **mismatch repair** system, which recognizes mismatched bases, distinguishes the newly synthesized strand, excises the incorrect region using endonucleases and exonucleases, and resynthesizes the correct sequence. **Excision repair** pathways correct damaged bases. **Base excision repair** removes chemically altered bases using glycosylases, followed by cutting the backbone and filling in the gap. **Nucleotide excision repair** removes bulky lesions such as thymine dimers by excising a short single-stranded DNA segment containing the damage. Endonucleases initiate the cut, and DNA polymerase and ligase restore the correct sequence. Defects in repair pathways can lead to elevated mutation rates and genomic instability. For example, mismatch repair defects are associated with hereditary colon cancer. Overall, the coordinated actions of proofreading, mismatch repair, and excision repair protect the integrity of the genome.

Answer 50

Chromosomal mutations can alter the number or structure of chromosomes, with **aneuploidy** and **polyploidy** being two major numerical abnormalities. **Aneuploidy** refers to the gain or loss of individual chromosomes and typically results from nondisjunction during meiosis. Common examples include **Down syndrome** (trisomy 21), which causes developmental delay; **Turner syndrome** (monosomy X), characterized by short stature and infertility; and **Klinefelter syndrome** (XXY), which leads to feminized features and infertility. Aneuploidy generally disrupts gene dosage balance, producing significant physiological effects. In contrast, **polyploidy** involves changes in the entire set of chromosomes (e.g., triploidy or tetraploidy). Polyploidy is rare and usually lethal in humans but common in plants, where it can result in increased size and vigor. Because whole sets of chromosomes are duplicated, gene dosage remains balanced within each set, making polyploidy more tolerated in some organisms. Both aneuploidy and polyploidy highlight the importance of proper chromosome segregation for normal development.

Answer 51

Crossing over is the exchange of genetic material between homologous chromosomes during prophase I of meiosis. The process begins when homologs pair and form synaptonemal complexes. Specific enzymes introduce double-strand breaks, and homologous recombination machinery facilitates the exchange of corresponding DNA segments. This produces **recombinant chromatids** that contain a mixture of maternal and paternal alleles. The significance of crossing over lies in its ability to generate new allele combinations, greatly enhancing genetic diversity within populations. This reshuffling of genetic information contributes to evolutionary adaptation and affects linkage relationships between genes. Proper crossing over is also essential for accurate chromosome segregation; insufficient recombination can lead to nondisjunction and aneuploidy. Thus, crossing over plays both a genetic and structural role in meiosis.

Answer 52

A **point mutation** is defined as a change in the nucleotide sequence of DNA that involves the **substitution, deletion, or insertion of a single base**. When these mutations occur within the protein-coding region of a gene, they can alter or impair the function of the resulting protein by changing its amino acid composition. The different types of point mutations and their effects on protein structure and function are detailed below: 1. Silent (Synonymous or Neutral) Mutations **Mechanism and Structure:** A silent mutation is a single base substitution that occurs in the coding region of a gene but **does not cause an amino acid change** in the resulting polypeptide chain. **Effect on Protein Function:** * These mutations typically occur at the **silent sites** of the genetic code, often found in the third position of the triplet. * They **do not cause an amino acid substitution** because the genetic code is **redundant** (or degenerate), meaning that most amino acids are specified by more than one triplet. * Consequently, if the amino acid composition remains unchanged, the mutation **may not necessarily alter or impair the function** of the protein. * *Example:* If the 'A' in the GAA triplet (which codes for Glutamic acid, Glu) is replaced by a 'G', the resulting GAG triplet will still code for Glu. 2. Missense (Non-Synonymous) Mutations **Mechanism and Structure:** A missense mutation is a point mutation that results in a single base substitution leading to a **change in a single amino acid**. **Effect on Protein Structure and Function:** * If the substituted amino acid has **similar chemical properties** to the original one, the change **may not have significant consequences** for the protein's structure or function. * However, if the substitution results in an amino acid with different properties, the function of the protein may be **altered or impaired**. These changes can range from having no effect to having **severe, even fatal, effects** on the individual carrying the mutation. * *Example:* Sickle cell anemia is a disease caused by a missense mutation where a point mutation in the 6th amino acid position of the hemoglobin molecule replaces **glutamic acid with valine**. 3. Nonsense Mutations **Mechanism and Structure:** A nonsense mutation is a point mutation that converts an amino acid-coding triplet into one of the three **stop codons** (TAA, TAG, or TGA). **Effect on Protein Structure and Function:** * At the corresponding stop codon on mRNA (e.g., UAA), protein synthesis **halts prematurely**. * This leads to the production of a **shorter (truncated) protein**. * In some cases, if the mutation occurs near the 3' end of the gene and not too many amino acids are lost, the resulting protein **may retain partial function**, although its activity is usually reduced. 4. Read-Through Mutations **Mechanism and Structure:** A read-through mutation occurs when a **stop codon** (e.g., TAA) **is converted into a codon that codes for an amino acid** (e.g., GAA for glutamic acid). **Effect on Protein Structure and Function:** * As a result, the translational machinery fails to stop translation and **continues reading non-coding regions** of the mRNA into amino acids. * This produces a **longer protein** than intended, which can **negatively affect its function**. 5. Frameshift Mutations (Insertion or Deletion) **Mechanism and Structure:** Frameshift mutations involve the **insertion or deletion of one or several nucleotides** (bases) from the protein-coding region of a gene. **Effect on Protein Structure and Function:** * Because the genetic code is **comma-free** (meaning triplets are not separated by signals), inserting or deleting a base alters the reading frame of all subsequent triplets **downstream** (in the 3' direction) from the mutation. * The genetic message thus becomes **nonsensical**, leading to the incorporation of **incorrect amino acids** and potentially resulting in the production of premature stop codons. * However, if the insertion or deletion involves **three (or a multiple of three) nucleotides**, the reading frame remains unchanged, and the protein may, in some instances, **retain its normal function**.

Answer 53

One of the gene mutations that Severe dominantly iheritated neurological disorder characterized by progressive neurodegeneration. => Caused by **excessive expansion of CAG triplets (often more than 35) in huntington gene (4th chromosome)**

Answer 54

**Definition**: Different structural forms (tautomers) of the nitrogenous bases in DNA. ** Explanation**: The keto form (e.g., of Thymine, T) is the common form. A rare shift to the enol form causes incorrect base pairing during replication; for instance, enol-T pairs with Guanine (G) instead of Adenine (A), leading to a mutation.

Answer 55

Definition: Mutations suggested to arise in a non-random manner, potentially contradicting the Darwinian principle that genetic variability is random and unrelated to future usefulness. Explanation: Examples include: Directed Global Mutations in bacteria under stress, where mutation rate increases (though changes remain random); Localized Hypermutations in Haemophilus influenzae where specific regions have exceptionally high mutation rates to evade the immune system; and Induced Local Mutations in E. coli where amino acid starvation increases mutation rate specifically in the defective gene.

Answer 56

Definition: A chemical species that promotes mutation by altering DNA structure. Explanation: Free radicals are mutagenic substances. Compounds such as peroxides are examples of mutagenic free radicals whose formation can be encouraged by indirectly acting chemicals.

2. DNA Flashcards

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