1. Genes and Chromosomes
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DNA Replication: A new role for a tumor-suppressing protein

  1. Jeremy S Setton Is a corresponding author
  2. Simon N Powell Is a corresponding author
  1. Memorial Sloan Kettering Cancer Center, United States
Cite as: eLife 2018;7:e35111 doi: 10.7554/eLife.35111
1 figure


Schematic showing the role of p53 at the replication fork.

When the DNA (black) replicates, the double helix opens to form a Y-shape called the replication fork. One new strand (the leading strand; green arrow) runs towards the replication fork, while the other (the lagging strand; green arrows at top) runs away from it. When a DNA lesion is encountered (in red), the replication fork may stall. Sometimes, however, the DNA continues to unwind ahead of the fork, leading to the formation of stretches of single-stranded DNA. This triggers a ‘replication-stress response’, which includes enlisting the protein p53 to the replication fork. In turn, p53 recruits MLL3 and then MRE11, which can modify the structure of nearby chromatin and prevent DNA breakage. This allows replication to restart and ensures that genetic information is preserved (genomic stability). Without p53, two proteins called RAD52 and Polθ are recruited to the stalled fork instead. Although these two proteins help to repair DNA, they can also lead to an accumulation of mutations (genomic instability).

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