Stalled forks

Here the authors demonstrate that the dsDNA binding function at the N-terminus of BRCA2 prevents nucleotide depletion-dependent replicative ssDNA gaps but not those induced by PARP inhibition. This function is impaired in breast-cancer variants affecting this region.

Kavlashvili et al. use a new in vitro approach to show that uncoupled replication forks can cause fork reversal and nascent strand degradation. Both processes occur without loss of the replisome from DNA and degradation involves multiple steps.

Subcellular localization plays an important yet underappreciated role in protein functions. Here the authors defined novel and context-dependent nuclear functions of the actin-binding factor profilin-1 in DNA replication fork dynamics and stability.

DNA replication stress can result in genome instability. Here the authors show that the ubiquitin like modifier protein, ISG15, important during the innate immune response, acts at replication forks to mitigate DNA replication stress.

Escherichia coli SSB enriches Pol IV polymerase at lesion-stalled replication forks, promoting translesion synthesis. Loss of this enrichment increases repriming of DNA synthesis, revealing a pivotal role of SSB in the pathway choice of stalled replication forks.

Non-camptothecin topoisomerase I inhibitor, Genz, shows potent activity against camptothecin-resistant cells through double-strand break induced cytotoxicity.