4.6 Review

RAD52: Paradigm of Synthetic Lethality and New Developments

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Summary: DNA replication is complex and filled with obstacles that require decisions on whether to bypass, repair, restart damaged forks, or protect stalled forks. The involvement of multiple proteins in repair and restart mechanisms is crucial, but questions remain on how to ensure faithful genome duplication and prevent destabilization of the genome leading to cancer, cell death, and chemotherapeutic resistance. Various key players, including PCNA, DNA polymerases, molecular motors, and proteins involved in homologous recombination, play important roles in determining the mechanisms utilized to maintain genome integrity during DNA replication.

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RAD52 Adjusts Repair of Single-Strand Breaks via Reducing DNA-Damage-Promoted XRCC1/LIG3α Co-localization

Jian Wang et al.

Summary: RAD52 deficiency increases cell survival after CPT treatment by inhibiting SSBR through its strong binding affinity to ssDNA and/or PAR. This neutralizes RAD52's role in DSBR, suggesting a balance between cell survival and genomic integrity. Blocking RAD52 oligomerization disrupts DSBR while retaining its ssDNA binding capacity, sensitizing cells to DNA-damaging agents and providing guidance for developing RAD52 inhibitors in cancer therapy.

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POLθ-mediated end joining is restricted by RAD52 and BRCA2 until the onset of mitosis

Marta Llorens-Agost et al.

Summary: BRCA2-deficient cells are vulnerable to inactivation of DNA repair pathways for DSBs, which can be exploited clinically. RAD52 and BRCA2 regulate the TMEJ process by blocking the POL theta function, ensuring proper repair of DSBs in mitosis.

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XAB2 promotes Ku eviction from single-ended DNA double-strand breaks independently of the ATM kinase

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XAB2 promotes Ku eviction from single-ended DNA double-strand breaks independently of the ATM kinase

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