Back

Mechanism of DNA-protein crosslink bypass by CMG helicase

Kyaw, M. T.; Xie, S.; de Lamo Peitz, E.; Yardimci, H.

2025-03-06 biochemistry
10.1101/2025.03.06.641852 bioRxiv
Show abstract

DNA-protein crosslinks (DPCs) pose significant barriers to DNA replication and genome integrity. Previous studies have established that bypass of DPCs by the eukaryotic replicative helicase, CMG complex, is critical for DPC repair. We investigated the mechanism of leading-strand DPC bypass by CMG using purified components. Our results reveal that CMG can bypass DPCs in the presence of downstream single-stranded DNA, without the aid of other replisome factors. DPC bypass is a slow process, and its efficiency depends on the size and structure of the protein barrier. DPC bypass does not require CMG to interact with the excluded strand or to unfold the protein adduct, implying that the CMG helicase ring opens to navigate past a DPC. Furthermore, opening of no single MCM interface is essential for bypass, suggesting a flexible ring opening mechanism. Our work highlights the remarkable versatility of the CMG complex in navigating replication challenges, ensuring proper replication fork progression and preserving genome stability.

Matching journals

The top 1 journal accounts for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.