protein localization to site of double-strand break

Definition

Target type: biologicalprocess

Any process in which a protein is transported to, or maintained at, a region of a chromosome at which a DNA double-strand break has occurred. [GOC:mah, PMID:23080121]

The intricate process of protein localization to sites of double-strand breaks (DSBs) in DNA is essential for the accurate repair of these damaging lesions. DSBs trigger a cascade of events involving the recruitment and assembly of numerous proteins, including DNA repair enzymes, signaling molecules, and chromatin remodeling factors. The precise choreography of this localization process ensures efficient and accurate DNA repair, safeguarding genomic integrity.

1. **Signal Generation and Sensing:** Upon DSB formation, the DNA ends are rapidly processed by nucleases, generating single-stranded DNA overhangs. These overhangs serve as signaling platforms for the recruitment of key DNA repair proteins.
2. **MRN Complex Recruitment:** The MRN complex (MRE11, RAD50, and NBS1) is among the first proteins to arrive at the DSB site. This complex possesses nuclease activity, contributing to the processing of DNA ends and also acts as a scaffold for subsequent protein recruitment.
3. **ATM Activation and Signaling:** The arrival of the MRN complex activates the ATM kinase, a key regulator of the DNA damage response. ATM phosphorylates a range of proteins, including histone H2AX, leading to the formation of γH2AX foci, which serve as a beacon for other repair factors.
4. **53BP1 and BRCA1 Recruitment:** 53BP1 and BRCA1 are two prominent proteins involved in the repair of DSBs through distinct pathways. 53BP1, a scaffold protein, recruits a suite of proteins to the DSB site, facilitating non-homologous end joining (NHEJ) repair. BRCA1, on the other hand, promotes homologous recombination (HR) repair by interacting with other proteins involved in the process.
5. **Chromatin Remodeling:** The recruitment of these proteins is accompanied by extensive chromatin remodeling. This involves changes in the structure of chromatin, allowing for the accessibility of DNA repair machinery to the damaged site.
6. **Scaffold Formation and Repair Initiation:** The coordinated assembly of these proteins at the DSB site results in the formation of intricate repair complexes. These complexes orchestrate the precise steps of DNA repair, such as resection, strand invasion, and ligation, ultimately restoring the integrity of the damaged DNA.

The localization of these proteins to DSBs is tightly regulated and relies on a complex network of protein-protein interactions, post-translational modifications, and signaling pathways. This sophisticated system ensures the rapid and efficient recruitment of the right proteins to the right place at the right time, enabling the accurate repair of DNA damage and maintaining genome stability.'
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Proteins (3)

Compounds (23)