Profound synthetic lethality between SMARCAL1 and FANCM.

DNA replication stress is a threat to genome integrity. The large SNF2-family of ATPases participates in preventing and mitigating DNA replication stress by employing their ATP-driven motor to remodel DNA or DNA-bound proteins. To understand the contribution of these ATPases in genome maintenance, we undertook CRISPR-based synthetic lethality screens in human cells with three SNF2-type ATPases: SMARCAL1, ZRANB3, and HLTF.

Genome-scale mapping of DNA damage suppressors through phenotypic CRISPR-Cas9 screens.

To maintain genome integrity, cells must accurately duplicate their genome and repair DNA lesions when they occur. To uncover genes that suppress DNA damage in human cells, we undertook flow-cytometry-based CRISPR-Cas9 screens that monitored DNA damage. We identified 160 genes whose mutation caused spontaneous DNA damage, a list enriched in essential genes, highlighting the importance of genomic integrity for cellular fitness.

RIF1-ASF1-mediated high-order chromatin structure safeguards genome integrity.

The 53BP1-RIF1 pathway antagonizes resection of DNA broken ends and confers PARP inhibitor sensitivity on BRCA1-mutated tumors. However, it is unclear how this pathway suppresses initiation of resection. Here, we identify ASF1 as a partner of RIF1 via an interacting manner similar to its interactions with histone chaperones CAF-1 and HIRA.

A Genetic Map of the Response to DNA Damage in Human Cells.

The response to DNA damage is critical for cellular homeostasis, tumor suppression, immunity, and gametogenesis. In order to provide an unbiased and global view of the DNA damage response in human cells, we undertook 31 CRISPR-Cas9 screens against 27 genotoxic agents in the retinal pigment epithelium-1 (RPE1) cell line. These screens identified 890 genes whose loss causes either sensitivity or resistance to DNA-damaging agents.

Colorimetric zearalenone assay based on the use of an aptamer and of gold nanoparticles with peroxidase-like activity.

An aptamer based colorimetric assay is described for the determination of zearalenone (ZEN). It is based on the inhibition of the peroxidase-mimicking activity of gold nanoparticles (AuNPs) by the ZEN aptamer. However, in the presence of ZEN, the aptamer is bound by ZEN and can no longer inhibit the peroxidase-mimicking activity of AuNPs.

An OB-fold complex controls the repair pathways for DNA double-strand breaks.

53BP1 with its downstream proteins, RIF1, PTIP and REV7, antagonizes BRCA1-dependent homologous recombination (HR) and promotes non-homologous end joining (NHEJ) in an unclear manner. Here we show that REV7 forms a complex with two proteins, FAM35A and C20ORF196. We demonstrate that FAM35A preferentially binds single-strand DNA (ssDNA) in vitro, and is recruited to DSBs as a complex with C20ORF196 and REV7 downstream of RIF1 in vivo.

Ewing Tumor-associated Antigen 1 Interacts with Replication Protein A to Promote Restart of Stalled Replication Forks.

The replication protein A (RPA) complex binds single-stranded DNA generated at stalled replication forks and recruits other DNA repair proteins to promote recovery of these forks. Here, we identify Ewing tumor-associated antigen 1 (ETAA1), which has been linked to susceptibility to pancreatic cancer, as a new repair protein that is recruited to stalled forks by RPA. We demonstrate that ETAA1 interacts with RPA through two regions, each of which resembles two previously identified RPA-binding domains, RPA70N-binding motif and RPA32C-binding motif, respectively.