Page last updated: 2024-10-24

mitotic recombination-dependent replication fork processing

Definition

Target type: biologicalprocess

Replication fork processing that includes recombination between DNA near the arrested fork and homologous sequences. Proteins involved in homologous recombination are required for replication restart. [GOC:mah, PMID:23093942]

Mitotic recombination-dependent replication fork processing is a crucial mechanism that ensures the faithful duplication of DNA during cell division. It occurs when a replication fork, the structure that replicates DNA, encounters a block or damage in the template DNA. This blockage can be caused by various factors, including DNA lesions, stalled replication forks, or topological stress.

When a replication fork stalls, it can activate a cascade of events involving multiple pathways, including homologous recombination (HR) and translesion synthesis (TLS). While TLS allows the replication machinery to bypass the lesion, HR serves to repair the damaged DNA segment and restore the original sequence.

In mitotic recombination-dependent replication fork processing, HR plays a crucial role in rescuing the stalled replication fork and promoting its progression. The process involves several steps:

1. **Strand Invasion and D-Loop Formation:** The stalled replication fork, unable to proceed, recruits proteins involved in HR, such as Rad51 and Rad54. These proteins mediate the invasion of the sister chromatid by the broken replication fork, forming a displacement loop (D-loop).

2. **Replication Fork Resumption:** The invaded sister chromatid acts as a template for the stalled replication fork to resume DNA synthesis. The original, damaged template strand is used as a template for the synthesis of a new complementary strand.

3. **Crossover Resolution:** The D-loop formed during strand invasion can lead to a Holliday junction, a four-way DNA junction that requires resolution. This resolution, mediated by enzymes like resolvases, results in the exchange of genetic material between the sister chromatids, leading to crossover recombination.

4. **Replication Fork Completion:** After the resolution of the Holliday junction, the replication fork continues to progress until it reaches the end of the chromosome. This ensures that the entire genome is replicated before cell division.

Mitotic recombination-dependent replication fork processing is an intricate process that allows cells to overcome replication stress and maintain genome integrity. By using the sister chromatid as a template for repair and replication, this mechanism ensures the faithful duplication of genetic information, which is essential for normal cell function and development.'
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Proteins (1)

ProteinDefinitionTaxonomy
DNA repair protein RAD51 homolog 1A DNA repair protein RAD51 homolog 1 that is encoded in the genome of human. [PRO:DNx]Homo sapiens (human)

Compounds (4)

CompoundDefinitionClassesRoles
5-hydroxyindolehydroxyindoleshuman metabolite
methyl tryptophan, (l-trp)-isomer
3-chloro-1-(2-chlorophenyl)-4-(4-morpholinyl)pyrrole-2,5-dionemaleimides
3-chloro-1-(3,4-dichlorophenyl)-4-(4-morpholinyl)-1h-pyrrole-2,5-dione3-chloro-1-(3,4-dichlorophenyl)-4-(4-morpholinyl)-1H-pyrrole-2,5-dione: an inhibitor of RAD51 that disrupts homologous recombination in human cells; structure in first source