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#genomic stability

3 public questions tagged with this topic.

Recombination

Ku70–Ku80 complex is involved in

Mammalian double-strand break repair choice depends on cell cycle and end processing factors. Ku70-Ku80 heterodimer is initial sensor avidly threading onto free DNA ends with sequence-independent high affinity, physically blocking extensive resection by MRN-CtIP and Exo1. By recruiting DNA-PKcs, XRCC4, Ligase IV, Ku drives classical non-homologous end joining pathway which re-ligates ends with minimal processing generating small indels. Loss of Ku unmasks ends to homologous recombination or alternative microhomology-mediated end joining, shifting repair balance toward resection-dependent mechanisms particularly active in S phase, illustrating competitive pathway control.

Ref: Lodish et al., Molecular Cell Biology, 9th ed., Chapter 12: Ku Complex Involvement in Classical NHEJ

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Recombination

BRCA2 assists homologous recombination by regulating

BRCA2 is prominent tumor suppressor containing BRC repeats that directly interact with Rad51. Under normal conditions RPA rapidly coats ssDNA preventing spontaneous Rad51 nucleation. After DNA damage, BRCA2 is recruited via PALB2 and BRCA1 to break sites where it mediates nucleation of Rad51 filament, stabilizing ATP-bound active conformation, blocking ATP hydrolysis mediated disassembly, and delivering Rad51 to ssDNA replacing RPA. This loader function is essential for strand invasion, D-loop formation, and homology-directed repair. Pathogenic BRCA2 mutations cause defective Rad51 recruitment, reliance on error-prone NHEJ, and breast-ovarian cancer susceptibility.

Ref: Lodish et al., Molecular Cell Biology, 9th ed., Chapter 19: BRCA2 Regulation of Rad51 Loading in HR

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Recombination

Rad51 functions in

Rad51 is eukaryotic ortholog of bacterial RecA and central recombinase for homologous recombination. Expression is not restricted to meiotic tissue; it operates in mitotic somatic cells repairing collapsed forks and double-strand breaks using sister chromatid template, and in meiotic cells alongside Dmc1. Rad51 forms presynaptic filament that executes homology search, invasion, and D-loop formation. Its activity regulated by mediators BRCA2, Rad52, and Rad51 paralogs that facilitate RPA displacement. Loss causes hypersensitivity to ionizing radiation, embryonic lethality, and cancer predisposition in both mitotic and meiotic contexts.

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 5: Rad51 Function in Mitosis and Meiosis

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