Bakkenist Lab

University of Pittsburgh at Pittsburgh

RADIATION-DIAGNOSTIC/ONCOLOGY

Pittsburgh · United States

NIH-funded
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NIH R01 · 2024

DNA damage signaling to dormant origins of replication

Higher eukaryotes evolved with mechanisms that initiate DNA replication at multiple origins on multiple chromosomes. Activation of the replicative helicase at a single origin in each of ~50,000 replicons is sufficient to replicate the human genome in the absence of stress. These ~50,000 origins are selected from a five- to tenfold excess of licensed origins. Activation of additional replicative helicases at origins that would otherwise be passively replicated is observed after stress. This plasticity in origin use is a simple mechanism to recover DNA replication between stalled and collapsed replication forks. The mechanism(s) that limits origin firing to one per replicon in the absence of…

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