A mutation eliminates the Shugoshin protein in a dividing cell. What is the most likely consequence during mitosis?
ACohesin fails to load onto chromosomes during S phase, causing premature sister separation before mitosis begins
BCentromeric cohesin is removed during prophase along with arm cohesin, causing sisters to separate before proper spindle attachment
CThe cell cannot enter anaphase because securin is not degraded by the APC/C
DChromosome condensation fails during prophase because arm cohesin removal is blocked
Shugoshin protects centromeric cohesin from Wapl-mediated removal during prophase. Without Shugoshin, Wapl removes centromeric cohesin simultaneously with arm cohesin, causing sisters to separate prematurely before the spindle has made proper bioriented attachments. This leads to random chromosome segregation and aneuploidy. The two-step release exists precisely to keep sisters connected at the centromere until the cell is ready to divide.
Question 2 Multiple Choice
Cohesin is described as holding sister chromatids together by 'topological entrapment.' What does this mean?
ACohesin forms a physical adhesive bond to the DNA backbone at multiple sites along the chromatid length
BThe cohesin ring encircles both sister chromatid DNA molecules so they are physically trapped inside the ring without covalent bonds to the DNA
CCohesin wraps tightly around the DNA helix to prevent strand separation under mechanical tension from the spindle
DCohesin uses ATP-dependent clamping to compress both chromatids together at defined intervals
The topological entrapment model means the ring physically surrounds both DNA molecules — they are threaded through the ring interior like two threads through a loop. This is distinct from chemical adhesion (option A) because the ring holds without covalent bonds and can be released simply by opening. This explains why separase cleavage of the SCC1 subunit is sufficient to release cohesion at anaphase: opening the ring allows the DNA molecules to fall out.
Question 3 True / False
Cohesin is loaded onto chromosomes after DNA replication is complete, so that both sister chromatids can be captured together once they exist.
TTrue
FFalse
Answer: False
Cohesin is loaded *during* S phase, as replication forks pass through — not after replication is complete. The timing is critical: cohesin must be established behind the replication fork so that newly synthesized sister chromatids are captured together the moment they emerge. Loading after replication would miss the window when the sisters are in close proximity and could be co-entrapped by the ring.
Question 4 True / False
The removal of arm cohesion during prophase requires the protease separase to cleave the SCC1 subunit of cohesin.
TTrue
FFalse
Answer: False
Prophase arm cohesion removal is mediated by *Wapl* — a regulatory protein that opens the cohesin ring — not separase. Separase is the protease responsible only for cleaving centromeric cohesin at the metaphase-to-anaphase transition, and it is held inactive by securin until APC/C activation. This two-step mechanism — Wapl removes arm cohesin, separase cleaves centromeric cohesin — is precisely what defines the two distinct stages of cohesion release.
Question 5 Short Answer
Why is the two-stage release of cohesin (arm cohesion in prophase, centromeric cohesion at anaphase) functionally important for accurate chromosome segregation?
Think about your answer, then reveal below.
Model answer: Arm cohesion removal during prophase allows chromosomes to condense into compact X-shaped structures accessible to the spindle, while retaining centromeric cohesion ensures sisters remain physically connected until the spindle has made proper bioriented attachments at both kinetochores. If all cohesion were released at once — or if centromeric cohesion were lost before biorientation — sisters could segregate randomly, producing aneuploidy. The two-step system couples the final cohesion release to the metaphase-to-anaphase checkpoint, ensuring separation only occurs when the cell is ready.
The spatial logic is key: Shugoshin protects only centromeric cohesin, so arm cohesin (distributed along chromosome arms) is removed first. This staged release trades some compaction benefit against the safety of keeping sisters tethered until the last moment — a design that minimizes segregation errors.