Reviewed by Simpal K. Suman(Biotech communicator)
DNA is a macro bio-molecule that carries genetic information and stands for Deoxyribo nucleic acid. In central dogma of molecular Biology DNA plays critical role. DNA metabolism includes DNA repair which maintained fidelity of DNA replication. DNA replication is highly regulated process and any mismatch leads to mutation. DNA exists under highly noise cellular environment and multiple factors affect them and mutation is its result .There are various inbuilt mechanisms that exists for DNA repair and protects its genomic integrity. Scientists are still trying to unmask these mechanisms to fully comprehend how these DNA repair processes are managed and regulated. In the context of DNA repair mechanism, scientists identified βarrestin-1(βarr1) mediated DNA repair.
Recently researchers from Moffitt Cancer Center identified a new mechanism that controls DNA repair. The paper is published in the journal Cell Death & Differentiation.
Previous research demonstrated that βarrestin-1(βarr1) controls p53 levels in response to catecholamine-induced chronic stress. As a result, this stress-induced βarr1 mediated genomic instability. βarr1 acting as a scaffold for the E3-ubiquitin ligase MDM2 that targets p53 for degradation.
In the current study, the researchers performed experiments to determine if the protein βarrestin1 (βarr1) plays any additional role in DNA damage repair. They discovered that βarr1 interacts with the p53-binding protein 1 (53BP1) via a multiprotein complex. 53BP1 is known to be key or principle component of the DNA damage response including DSB(DNA strand breaks). The interaction between βarr1 & 53BP1 causes 53BP1 to be targeted for protein degradation( p53 ) , as a result reducing its ability to repair DNA. Notably, the researchers also demonstrated that mice lacking βarr1 survived longer time length under the presence of ionizing radiation(IR) exposure than normal control mice. This demonstrated that loss of βarr1 expression is linked with radiation resistance to the toxic effects of radiation treatment/exposure.
Moffitt Cancer Center
Nieto, A. et al. (2019) βarrestin-1 regulates DNA repair by acting as an E3-ubiquitin ligase adaptor for 53BP1. Cell Death & Differentiation.