Current Understanding of RAD52 Functions: Fundamental and Therapeutic Insights

Vanesa Gottifredi,Lisa Wiesmüller

doi:10.3390/cancers12030705

Abstract

In this Special Issue, we would like to focus on the various functions of the RAD52 helicase-like protein and the current implications of such findings for cancer treatment. Over the last few years, various laboratories have discovered particular activities of mammalian RAD52—both in S and M phase—that are distinct from the auxiliary role of yeast RAD52 in homologous recombination. At DNA double-strand breaks, RAD52 was demonstrated to spur alternative pathways to compensate for the loss of homologous recombination functions. At collapsed replication forks, RAD52 activates break-induced replication. In the M phase, RAD52 promotes the finalization of DNA replication. Its compensatory role in the resolution of DNA double-strand breaks has put RAD52 in the focus of synthetic lethal strategies, which is particularly relevant for cancer treatment.

Highlights

This Special Issue gathers experts in the field to convey both comprehensive, insightful, and current perspectives on the different functions of human RAD52 in the maintenance of genomic integrity and the current implications of such findings for cancer treatment
2000, it became clear that in mammalian cells, BRCA2 had taken over the RAD51-chaperoning activity, stimulating filament formation on single-stranded DNA, while RAD52 was left with the single-strand annealing (SSA) activity [2]
RAD52 research has seen a renaissance in recent years after the disappointment linked to the discovery of mammalian RAD52 playing a subordinate role to BRCA2 in human cells, i.e., an at-most minor role in homologous recombination (HR)

Summary

Introduction

This Special Issue gathers experts in the field to convey both comprehensive, insightful, and current perspectives on the different functions of human RAD52 in the maintenance of genomic integrity and the current implications of such findings for cancer treatment. DSB repair, which may play a role during transcription, replication, class-switch structures like R loops in unprecedented homology-directed DSB repair events [9]. RAD52- and RPA-mediated homology-directed loops during found to bereplication, bound by CSB, followedrecombination, by RAD52-mediated, repair,generated which may playtranscription a role duringwere transcription, class-switch and at BRCA-independent. RAD52protection activates break-induced replication when itofcounteracts excessive fork regression, whichforks, may exhaust factors, causing replication (BIR), a specialized pathway that repairs single-ended. XPG that have reverted to process these structures into substrates, enabling the cell to during TA-HR It cooperates with MRE11 and MUS81/EME1 at de-protected forks that have continue replication [10,11,12].

Multiple

Conclusions