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II. Dynamic Localization of BER Proteins
A. General Pathway
In general, dynamic localization of BER proteins functions through the
generation of an organellar-specific signal which recruits the required BER
proteins to the organelle where DNA damage has occurred ( Fig. 1 ). As BER
proteins are responsible for maintenance of both nuclear and mitochondrial
genomes, there is competition between the nucleus and the mitochondria for a
rather small pool of BER proteins. The advantage of such a mechanism is an
extremely rapid response to increased cellular stress which does not require
new transcription and translation of BER genes and instead utilizes the overall
low level of BER proteins normally present.
B. Requirements to Dynamically Localize
In order for dynamic localization to occur, a few requirements must be met.
The first requirement is the generation of a signaling event to initiate dynamic
localization. Such an event originates in response to different types of DNA
damage including, but not limited to, oxidative DNA damage and alkylation
damage. 39 The specific type of DNA damage may dictate which proteins are
mobilized by dynamic localization. However, for proteins in the BER pathway
to initially respond and be regulated by dynamic localization, they must first
F IG . 1. General model of dynamic localization for base excision repair (BER) proteins. Protein
X is any BER protein able to localize to both nuclei and mitochondria (black arrows). Under DNA-
damaging conditions, organelle-specific signals are generated, originating from either the mito-
chondria (red arrows) or nuclei (blue arrows) depending upon the relative threat to organelle
genome stability. These signals result in competition between mitochondria (red arrows) and nuclei
(blue arrows) for protein X driving economical localization BER protein for efficient DNA repair.
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