RI 1, RAD51 inhibitor

Supplementary information

This supplementary information is collated from multiple sources and compiled automatically.

Rad51 Rad1 and BFL-1/GRS are essential proteins involved in DNA repair and apoptosis regulation. Rad51 also known as RAD51A is a 37 kDa protein that facilitates homologous recombinational repair of DNA during double-strand break events. It is generally expressed in a variety of tissues especially in dividing and stressed cells. Rad1 with a mass of approximately 31 kDa is a checkpoint protein that plays a role in the maintenance of genomic integrity. It forms part of the 9-1-1 complex and is expressed in the nucleus. BFL-1 also known as GRS is part of the Bcl-2 protein family and weighs around 17 kDa. This protein is found primarily in immune and cancerous cells.

Biological function summary

The homologous recombination process heavily relies on Rad51. It achieves this by promoting strand exchange stabilizing nucleoprotein filaments and facilitating DNA synapsis. Rad1 is a component of the 9-1-1 checkpoint complex which functions like a sliding clamp and is important during the DNA damage response helping halt the cell cycle to allow repair. BFL-1/GRS plays an integral part in cell survival mechanisms by inhibiting apoptosis through the interaction with pro-apoptotic members of the Bcl-2 family. It thereby ensures that cells bypass apoptotic signals under stress conditions.

Pathways

Rad51 operates mainly within the homologous recombination repair pathway an important process for error-free DNA repair and genome stability. It interacts closely with proteins like BRCA1 and BRCA2 which assist in its recruitment and function. Rad1 is a significant player in the cell cycle checkpoint pathway specifically through its involvement with the ATR-Claspin pathway which is pivotal for the activation of downstream signals such as Chk1. BFL-1/GRS engages in the regulation of the intrinsic apoptotic pathway interacting with proteins like Bak and Bax modulating mitochondrial outer membrane permeabilization.

Rad51 mutations or dysregulation link to various cancers particularly breast and ovarian cancers due to compromised DNA repair mechanisms. Rad51 works with BRCA2 mutations that demonstrate a similar disease association. On the other hand Rad1 malfunctions can contribute to genomic instability leading to syndromes like Ataxia Telangiectasia. BFL-1/GRS has connections to chemotherapy resistance in cancers due to its anti-apoptotic properties. It relates to Mcl-1 another Bcl-2 family member known for its role in similarly preventing apoptosis and contributing to cancer cell survival.