Preserving the Replication Fork in Response to Nucleotide Starvation: Evading the Replication Fork Collapse Point

Replication fork progression is blocked by a variety impediments including DNA damage, aberrant DNA structures, or nucleotide depletion [1-3]. The response to replication fork stalling varies according the type of replication inhibition, the number of stalled forks and the duration of the treatment [3-7]. Stalled replication forks are at increased risk for DNA damage, which can lead to mutation or cell death [7-13]. The cell relies on the Intra-S phase checkpoint and DNA damage response proteins to preserve fork structure to allow recovery and resumption of the cell cycle [5, 10, 14-19]. Thus, the mechanisms that maintain replica‐ tion fork structure are crucial for genome maintenance, and form a primary barrier to malig‐ nant transformation [20, 21].