21.single -strand nick in parental DNA helix just ahead of a replication fork causesthe replication fork to break. Recovery from this calamity requires
(1) DNA ligase
(2) DNA primase
(3) Site-specific recombination
(4) homologous recombination

• • Single-strand nick and replication fork collapse

  • Homologous recombination in DNA repair

  • DNA double-strand break repair

  • Replication fork recovery mechanisms

  • DNA damage tolerance and repair

  • RecA and Rad51 proteins

  • Genome stability and replication stress

  • DNA repair pathways in replication

  • DNA strand invasion and repair synthesissingle -strand nick in parental DNA helix just ahead of a replication fork causesthe replication fork to break. Recovery from this calamity requires
    (1) DNA ligase
    (2) DNA primase
    (3) Site-specific recombination
    (4) homologous recombination

    Recovery from Replication Fork Breakage Caused by a Single-Strand Nick Ahead of the Fork Requires Homologous Recombination

    During DNA replication, the replication fork progresses along the parental DNA strands to synthesize new daughter strands. However, if a single-strand nick exists in the parental DNA just ahead of the replication fork, this can cause the fork to collapse or break, resulting in a double-strand break (DSB). This breakage poses a serious threat to genome stability and cell survival.

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    What Happens When a Single-Strand Nick Causes Fork Breakage?

    • The replication machinery encounters the nick and the fork collapses, producing a one-ended double-strand break.

    • This break cannot be repaired by simple ligation or direct repair because the DNA is broken and lacks a complementary strand at the break site.

    • The cell must employ specialized repair pathways to restore the fork and resume replication.

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    Repair Mechanism for Replication Fork Breakage: Homologous Recombination

    Homologous recombination (HR) is the primary and error-free pathway used to repair replication fork breakage caused by single-strand nicks ahead of the fork. Key features include:

    • Strand invasion: The broken DNA end invades the intact sister chromatid (the newly synthesized identical DNA duplex), using it as a template for repair.

    • DNA synthesis: DNA polymerases extend the invading strand, restoring the missing information.

    • Resolution: The recombination intermediates are resolved, allowing replication to restart.

    This process effectively restores the replication fork structure and maintains genomic integrity.

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    Why Other Options Are Not Correct

    • DNA ligase:

      • Ligase seals nicks in DNA but cannot repair a broken replication fork caused by a double-strand break.

    • DNA primase:

      • Primase synthesizes RNA primers during replication but does not repair broken forks.

    • Site-specific recombination:

      • This mechanism involves recombination at specific DNA sequences and is not the general repair pathway for replication fork breakage.

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    Supporting Evidence from Research

    • Studies show that replication fork collapse due to nicks leads to one-ended DSBs repaired by HR (PMCID: PMC8098667).

    • HR proteins such as RecA in bacteria and Rad51 in eukaryotes mediate strand invasion and repair synthesis at broken forks.

    • Alternative pathways like fork reversal and translesion synthesis may help tolerate damage but cannot repair fork breakage itself.

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    Summary Table

    Repair Factor	Role in Fork Breakage Recovery	Suitable for Repair of Fork Breakage?
    DNA ligase	Seals nicks	No
    DNA primase	Synthesizes RNA primers	No
    Site-specific recombination	Recombination at specific sites	No
    Homologous recombination	Repairs DSBs using sister chromatid	Yes

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    Correct Answer

    (4) Homologous recombination

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