Abstract
Mammalian Radiation Sensitive 52 (RAD52) is a gene whose scientific reputation has recently seen a strong resurgence. In the past decade, RAD52, which was thought to be dispensable for most DNA repair and recombination reactions in mammals, has been shown to be important for a bevy of DNA metabolic pathways. One of these processes is termed break-induced replication (BIR), a mechanism that can be used to re-start broken replication forks and to elongate the ends of chromosomes in telomerase-negative cells. Viruses have historically evolved a myriad of mechanisms in which they either conscript cellular factors or, more frequently, inactivate them as a means to enable their own replication and survival. Recent data suggests that Adeno-Associated Virus (AAV) may replicate its DNA in a BIR-like fashion and/or utilize RAD52 to facilitate viral transduction and, as such, likely conscripts/requires the host RAD52 protein to promote its perpetuation.
Highlights
Pathways of DNA Double-Stranded Break RepairDNA double-stranded breaks (DSBs) are the most toxic form of genomic lesions for human cells
Mammalian Radiation Sensitive 52 (RAD52) is a gene whose scientific reputation has recently seen a strong resurgence
To ensure that double-stranded breaks (DSBs) are repaired, mammals have developed at least two major pathways of DSB repair—classic non-homologous end joining (C-NHEJ; Figure 1A) [2] and homology-directed repair (HDR; Figure 1C) [3]—that are differentially utilized depending upon the actual DSB lesion, the stage of the cell cycle and the organism in which the lesion occurs [4,5]
Summary
DNA double-stranded breaks (DSBs) are the most toxic form of genomic lesions for human cells. These lesions can arise from both endogenous DNA replication errors and via exogenous exposure to agents that damage DNA. The toxicity of DSBs is so profound that even a single unrepaired. DSB can lead to cell death [1]. DSB repair in toto is an exceptionally complicated process that requires literally hundreds of different factors in order to be accomplished successfully. One of these factors, RAD52, will be the focus of this review
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