59. The following statements are made With reference to DNA replication:
60. Camptothecin causes intra- strand and jnter-strand crosslinks in DNA, leading to stalling of replication forks.
61. Prevention of re-initiation of DNA replicationduring the same cell cycle is mediated by regulating the loading of the initiator complex ORC                                                                                                                                                                                                                         A gluà ala mutation in the nucleotide building pocket of DNA polymerase III could lead to the incorporation of ribonucleotides in the extending DNA chain                                                                                                                                                                                          A mutation in the gene encoding Topoisomerase II could lead to entanglement of DNA daughter strands during replication.

Which one of the following options represents all correct statements?

(1) A and B only      (2) B and C only

(3) C and D only      (4) B, C and D only

Statement-by-Statement Evaluation

A. Camptothecin causes intra-strand and inter-strand crosslinks in DNA, leading to stalling of replication forks.

• Camptothecin (CPT) is a topoisomerase I inhibitor that stabilizes the covalent Topo I-DNA complex, causing replication fork stalling and double-strand breaks.

• However, CPT does not cause intra-strand or inter-strand crosslinks; those are caused by other agents like cisplatin.

• CPT causes DNA damage by trapping Topo I cleavage complexes, leading to fork collapse, not crosslinks.

• Therefore, Statement A is incorrect.

B. Prevention of re-initiation of DNA replication during the same cell cycle is mediated by regulating the loading of the initiator complex ORC.

• The Origin Recognition Complex (ORC) is involved in origin licensing during G1 phase.

• Prevention of re-replication involves multiple mechanisms, including regulation of ORC, Cdc6, Cdt1, and geminin.

• ORC regulation is a key step in preventing re-initiation within the same cell cycle.

• Statement B is correct.

C. A glu→ala mutation in the nucleotide binding pocket of DNA polymerase III could lead to the incorporation of ribonucleotides in the extending DNA chain.

• DNA polymerase III normally discriminates against ribonucleotides during DNA synthesis.

• Mutations in the nucleotide binding pocket can reduce this discrimination, allowing ribonucleotide incorporation.

• A glutamate to alanine substitution could alter binding specificity.

• Statement C is correct.

D. A mutation in the gene encoding Topoisomerase II could lead to entanglement of DNA daughter strands during replication.

• Topoisomerase II resolves DNA tangles and supercoils by creating transient double-strand breaks.

• Mutation or loss of Topo II function impairs decatenation of daughter chromatids, leading to entanglement.

• Statement D is correct.

Summary Table

Final Answer

(4) B, C and D only

Keywords

camptothecin, DNA replication fork stalling, origin recognition complex, DNA polymerase III mutation, ribonucleotide incorporation, topoisomerase II, chromosome entanglement, DNA replication regulation

Conclusion

Among the given statements, only A is incorrect because camptothecin does not cause DNA crosslinks but rather stabilizes Topo I-DNA complexes, leading to replication fork stalling and DNA breaks. Statements B, C, and D are correct, reflecting current understanding of replication initiation control, polymerase fidelity, and topoisomerase function in chromosome segregation.

Correct option:
(4) B, C and D only