Genome Sweet Genome
What are homologous chromosomes, and how can they differ despite carrying the same genes?
Homologous chromosomes are a pair of chromosomes with the same genes at similar loci, lengths, and positions. but they can contain different alleles and have different DNA sequences
What are the three phases of interphase, and what major cellular activities occur during each?
G1: The cell synthesizes proteins, RNA, and lipids in preparation for division.
S: DNA replication occurs, producing sister chromatids.
G2: The cell prepares for chromosome segregation, including DNA repair and proofreading.
How many histone proteins form the core of a nucleosome, and approximately how many times does DNA wrap around this structure?
A nucleosome contains eight histone proteins, forming a histone octamer. DNA wraps around this histone core approximately 1.65 times. The histone octamer contains two copies each of H2A, H2B, H3, and H4. This arrangement allows DNA to become compact while remaining organized for cellular processes such as transcription and replication.
In which direction does DNA polymerase synthesize new DNA, and to which end of the growing strand are nucleotides added?
DNA polymerase synthesizes DNA in the 5′ to 3′ direction by adding nucleotides to the free 3′ hydroxyl (OH) group of the growing strand. This means that the DNA template is read in the opposite direction, 3′ to 5′.
What is the difference between the leading strand and the lagging strand during DNA replication?
The leading strand is synthesized continuously in the direction of replication fork movement and generally requires one RNA primer. The lagging strand is synthesized discontinuously, away from the direction of fork movement, in short sections called Okazaki fragments. Both strands are synthesized in the 5′ to 3′ direction because DNA polymerase can add nucleotides only to a free 3′ hydroxyl group
A single human cell contains approximately two meters of DNA. How is this DNA organized to fit inside the nucleus?
DNA wraps around histones that are postive charged to form nucleosomes that create chromatin, this can protein can create compaction of dna and condense the chromosome during cell division
What is the difference between chromatin, a chromosome, and a chromatid?
Chromatin: DNA associated with histone proteins and organized into nucleosomes.
Chromosome: An organized DNA structure that can become highly condensed during mitosis.
Chromatid: One of the two DNA copies of a replicated chromosome. The identical copies are called sister chromatids and remain associated until they separate during mitosis.
What is the role of histone H1 in DNA compaction, and how does it differ from the histones forming the nucleosome core?
Histone H1 is a positively charged linker histone that interacts with DNA near the entrance and exit of a nucleosome, including linker DNA between nucleosomes. Unlike H2A, H2B, H3, and H4, H1 is not part of the eight-protein nucleosome core. Instead, it helps stabilize additional chromatin compaction.
DNA polymerase is often compared to a right hand. What are its three major domains, and which domain directly contains the catalytic site?
And what happens to the fingers domain of DNA polymerase when an incoming nucleotide correctly base-pairs with the template?
The three domains are the palm, fingers, and thumb. The palm contains the catalytic site, where nucleotide addition occurs. The fingers interact with incoming nucleotides and the template, while the thumb helps position the newly synthesized DNA and maintain polymerase attachment.
When the correct nucleotide forms a base pair with the template, the fingers domain closes around it. This conformational change positions the incoming dNTP near the catalytic metal ions, allowing the chemical reaction that incorporates the nucleotide into the DNA strand.
What is the function of primase, and why is this enzyme necessary for DNA replication?
Primase synthesizes short RNA primers on the DNA template. These primers provide the free 3′ hydroxyl group required for DNA polymerase to begin nucleotide addition. DNA polymerase cannot initiate new DNA strands on its own, but primase can synthesize RNA de novo, meaning it can begin making a new strand without an existing primer.
Two DNA sequences are located within the same gene. One remains in the mature mRNA, while the other is removed during RNA splicing. What are these two sequence types, and how do they differ?
The retained sequence is an exon, while the removed sequence is an intron. Exons remain in mature RNA and may contain protein-coding information or untranslated regions. Introns are transcribed into precursor RNA but are generally removed during splicing before translation.
What two major events involving cohesin and microtubules occur during anaphase?
During anaphase, cohesin is broken down, allowing sister chromatids to separate. Kinetochore microtubules help move the separated chromatids toward opposite poles, while non-kinetochore (interpolar) microtubules elongate, helping stretch the cell. These processes distribute the duplicated genetic material between the developing daughter cells.
Why are DNA binding sites located near the ends of nucleosomes generally more accessible than binding sites near the center?
DNA is wrapped around histones through multiple interactions, but these interactions are transient. DNA near the ends of a nucleosome can temporarily separate from the histone core more easily because fewer interactions must be disrupted.
What type of chemical reaction adds a new nucleotide to DNA, and which molecular group initiates the reaction?
Nucleotide addition occurs through an SN2-type nucleophilic substitution reaction. The 3′ hydroxyl group on the growing DNA strand attacks the alpha phosphate of the incoming dNTP.
This creates a new phosphodiester bond, extending the DNA strand by one nucleotide and releasing pyrophosphate.
After an Okazaki fragment has been synthesized, what enzymes are involved in removing its RNA primer, replacing it with DNA, and sealing the remaining break?
RNase H removes most of the RNA primer by cleaving phosphodiester bonds within the RNA portion of the RNA-DNA hybrid.
A 5′ exonuclease removes the remaining RNA nucleotide.
DNA polymerase fills the resulting gap with DNA.
DNA ligase seals the remaining nick in the DNA backbone by forming a phosphodiester bond.
A mutation damages a chromosome's centromere, preventing proper kinetochore formation. How could this affect cell division?
The centromere is the chromosomal region where the kinetochore assembles. The kinetochore connects chromosomes to spindle microtubules, allowing sister chromatids to be separated during mitosis. If a functional kinetochore cannot form, the chromosome may fail to attach or segregate correctly, potentially producing daughter cells with abnormal chromosome numbers.
A cell enters anaphase, but its cohesin complex is not broken down. Predict how this would affect chromosome segregation.
Cohesin normally holds sister chromatids together and must be broken down during anaphase to allow separation.
If cohesin remains intact, sister chromatids cannot separate properly even when spindle microtubules pull toward opposite poles. This interferes with chromosome segregation and could prevent the daughter cells from receiving complete, correctly distributed chromosome sets.
What enzymes add and remove acetyl and methyl groups from histones, and why are these modifications important?
Histone acetyltransferases (HATs): Add acetyl groups.
Histone deacetylases (HDACs): Remove acetyl groups.
Histone methyltransferases (HMTs): Add methyl groups.
Histone demethylases (HDMs): Remove methyl groups.
These modifications can influence chromatin structure and create binding sites for proteins that regulate gene expression.
What is the function of the sliding DNA clamp, and how does it increase DNA polymerase processivity?
The sliding clamp forms a ring around DNA and helps retain DNA polymerase near the primer-template junction. Without the clamp, DNA polymerase may dissociate after adding relatively few nucleotides. The clamp prevents the enzyme from diffusing away easily and allows it to resume synthesis at the same junction.
Why are multiple origins of replication necessary on eukaryotic chromosomes, and what could happen if some origins fail to activate?
Eukaryotic chromosomes are extremely long, so replication initiates at multiple origins, allowing different sections of DNA to be copied simultaneously.
A chromosome develops a second functional centromere. Explain why this could be dangerous during mitosis and what might happen to the chromosome.
A chromosome containing two functional centromeres is called a dicentric chromosome. If both centromeres attach to spindle microtubules pulling toward opposite poles, the chromosome may experience opposing forces during anaphase.
This can form a chromosome bridge, potentially causing DNA breakage, chromosome rearrangements, or improper distribution of genetic material to daughter cells. The result may be genomic instability. Some dicentric chromosomes can remain stable if one centromere becomes inactive.
A cell completes DNA replication and begins mitosis. Explain how the functions of cohesin, condensin, kinetochores, and spindle microtubules must work together to ensure that each daughter cell receives the correct genetic information.
Cohesin: Holds newly replicated sister chromatids together until anaphase.
Condensin: Compacts chromosomes so they can be organized and separated efficiently.
Kinetochores: Connect the centromeres of sister chromatids to spindle microtubules.
Spindle microtubules: Establish proper attachment to opposite poles and help separate chromatids during anaphase.
Once sister chromatids are properly attached to opposite poles, cohesin is broken down, allowing the spindle to separate the chromatids. Together, these mechanisms help ensure that each daughter cell receives a complete chromosome set.
During DNA replication, nucleosomes must be temporarily disassembled. Explain how the conservation of existing histones helps daughter DNA molecules maintain information about their previous chromatin state.
: During DNA replication, nucleosomes are disrupted so replication machinery can access DNA. H3–H4 tetramers remain associated with DNA, while H2A–H2B dimers can enter a pool of free histones. Modified histones help preserve information about the original chromatin state. Their chemical modifications can recruit enzymes that establish similar modifications on neighboring newly incorporated histones.
How can changes in the chemical structure of DNA bases cause replication errors even when DNA polymerase normally selects nucleotides through complementary base pairing?
DNA bases can undergo tautomerization, a temporary rearrangement involving the movement of protons and electrons. These changes can alter a base's hydrogen-bonding properties, allowing it to pair with an incorrect nucleotide. Because DNA polymerase relies heavily on base-pairing geometry and hydrogen bonding to select the correct nucleotide, it can sometimes incorporate a rare tautomeric form incorrectly. If the error is not corrected, it may become a permanent mutation during replication.
Why does conventional DNA replication create a problem at the ends of linear chromosomes, and how does telomerase help solve this problem?
Conventional DNA polymerase requires an existing primer with a free 3′ hydroxyl group. When the final RNA primer is removed from the end of a newly synthesized lagging strand, there may be no upstream 3′ hydroxyl available for DNA polymerase to fill the remaining gap.