The single-stranded DNA-binding factor SUB1/PC4 alleviates replication stress at telomeres and is a vulnerability of ALT cancer cells.

To achieve replicative immortality, cancer cells must activate telomere maintenance mechanisms. In 10 to 15% of cancers, this is enabled by recombination-based alternative lengthening of telomeres pathways (ALT). ALT cells display several hallmarks including heterogeneous telomere length, extrachromosomal telomeric repeats, and ALT-associated PML bodies.

SMARCAL1 ubiquitylation controls its association with RPA-coated ssDNA and promotes replication fork stability.

Impediments in replication fork progression cause genomic instability, mutagenesis, and severe pathologies. At stalled forks, RPA-coated single-stranded DNA (ssDNA) activates the ATR kinase and directs fork remodeling, 2 key early events of the replication stress response. RFWD3, a recently described Fanconi anemia (FA) ubiquitin ligase, associates with RPA and promotes its ubiquitylation, facilitating late steps of homologous recombination (HR).

The mutational impact of Illudin S on human cells.

Illudin S (ILS) is a fungal sesquiterpene secondary metabolite with potent genotoxic and cytotoxic properties. Early genetic studies and more recent genome-wide CRISPR screens showed that Illudin-induced lesions are preferentially repaired by transcription-coupled nucleotide excision repair (TC-NER) with some contribution from post-replication repair pathways. In line with these results, Irofulven, a semi-synthetic ILS analog was recently shown to be particularly effective on cell lines and patient-derived xenografts with impaired NER (e.

Biogas production from high solids anaerobic co-digestion of food waste, yard waste and waste activated sludge.

High-solids anaerobic co-digestion (HS-AcD) has the potential to recover energy and reduce environmental impacts of the organic fraction of municipal solid waste and waste activated sludge. We investigated the impact of substrate to inoculum (S/I) ratios, alkalinity sources (sodium bicarbonate and oyster shells), co-substrate mixing ratios and inoculum acclimation on HS-AcD of food waste, yard waste, and waste activated sludge using batch studies. Long-term HS-AcD performance was evaluated under the optimal conditions through a semi-continuous biodigester study with leachate recirculation.