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R-loop-mediated genome instability in mRNA cleavage and polyadenylation mutants.
TLDR
It is found that truncation fusions of yeast FIP1 analogous to those in cancer cause loss of function and that siRNA knockdown of FIP 1L1 in human cells increases DNA damage and chromosome breakage.
Chromatid cohesion defects may underlie chromosome instability in human colorectal cancers
TLDR
It is shown that down-regulation or genetic disruption of the two major candidate CIN genes identified in previous studies also resulted in abnormal sister chromatid cohesion in human cells, suggesting that defective sister chrom atid cohesion as a result of somatic mutations may represent a major cause of chromosome instability in human cancers.
Synthetic Lethality of Cohesins with PARPs and Replication Fork Mediators
TLDR
This work demonstrates that large-scale genetic interaction screening in yeast can identify clinically relevant genetic interactions and suggests that PARP inhibitors, which are currently undergoing clinical trials as a treatment of homologous recombination-deficient cancers, may be effective in treating cancers that harbor cohesin mutations.
Specific synthetic lethal killing of RAD54B-deficient human colorectal cancer cells by FEN1 silencing
TLDR
It is demonstrated that RAD54B-deficient human colorectal cancer cells are sensitive to SL killing by reduced FEN1 expression, while isogenic RAD 54B proficient cells are not, which suggests that extrapolating SL interactions observed in model organisms for homologous genes mutated in human cancers will aid in the identification of novel therapeutic targets for specific killing of cancerous cells exhibiting CIN.
An Evolutionarily Conserved Synthetic Lethal Interaction Network Identifies FEN1 as a Broad-Spectrum Target for Anticancer Therapeutic Development
TLDR
Chemical-genetic interactions in mammalian cells validate evolutionarily conserved synthetic lethal interactions and demonstrate that a cross-species candidate gene approach is successful in identifying small-molecule inhibitors that prove effective in a cell-based cancer model.
Genome-Wide Synthetic Lethal Screens Identify an Interaction Between the Nuclear Envelope Protein, Apq12p, and the Kinetochore in Saccharomyces cerevisiae
TLDR
This study, which is the first example of genome-wide synthetic lethal screening with multiple alleles of a single gene, demonstrates that functionally distinct mutants uncover different cellular processes required for chromosome maintenance.
YB-1 evokes susceptibility to cancer through cytokinesis failure, mitotic dysfunction, and HER2 amplification
TLDR
A model of pre-malignancy to characterize the role of this gene during breast cancer initiation and early progression recognizes YB-1 as a cancer susceptibility gene, with the capacity to prime cells for tumorigenesis.
3 Aminobenzamide, an inhibitor of poly ADP-ribose polymerase, decreases the frequency of alkaline labile lesions and increases growth in human fibroblasts exposed to 3-methyl 4-nitroquinoline 1-oxide
TLDR
The data presented suggest an additional role for poly ADP ribose polymerase in DNA repair other than that of inhibiting the increase in ligase II, which occurs after exposure to monofunctional alkylating agents.
Lead Optimization of Benzoxepin-Type Selective Estrogen Receptor (ER) Modulators and Downregulators with Subtype-Specific ERα and ERβ Activity.
TLDR
A docking study of the benzoxepin ligands was undertaken and compound 13e is a promising lead for development as a clinically relevant SERD, while compound 22 will be a useful experimental probe for helping to elucidate the role of ERβ in cancer cells.
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