The roles of non-productive complexes of DNA repair proteins with DNA lesions

Abstract

A multitude of different types of lesions is continuously introduced into the DNA inside our cells, and their rapid and efficient repair is fundamentally important for the maintenance of genomic stability and cellular viability. This is achieved by a number of DNA repair systems that each involve different protein factors and employ versatile strategies to target different types of DNA lesions. Intriguingly, specialized DNA repair proteins have also evolved to form non-functional complexes with their target lesions. These proteins allow the marking of innocuous lesions to render them visible for DNA repair systems and can serve to directly recruit DNA repair cascades. Moreover, they also provide links between different DNA repair mechanisms or even between DNA lesions and transcription regulation. I will focus here in particular on recent findings from single molecule analyses on the alkyltransferase-like protein ATL, which is believed to initiate nucleotide excision repair (NER) of non-native NER target lesions, and the base excision repair (BER) enzyme hOGG1, which recruits the oncogene transcription factor Myc to gene promoters under oxidative stress.

Keywords: Atomic force microscopy (AFM); DNA repair; Fluorescence coupled optical tweezers; Protein-DNA interactions; Single molecule.