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Note for: Systematic E2 screening reveals a UBE2D-RNF138-CtIP axis promoting DNA repair (doi: 10.1038/ncb3260) Very nice piece of work, I would say. It reflects the complexity of living thing is, especially, post-translational modification processes which control the cellular function through adding the small molecule namely ubiquitin to certain protein. Unrepaired DSB -- genome instability, tumorigenesis, neurodegeneration or premature ageing. The team used UBE2Ds to screen for the binding partner during the DSB responses (using IR in this case). This study found RNF138 was the binding partner for UBE2Ds during the DSB responses. RNF138 promotes CtIF ubiquitination. Key to initiating HR is DNA-end resection promoted by CtIP (RBBP8) recruitment to DSB sites, yielding single-stranded DNA (ssDNA) that is rapidly bound by RPA and subsequently replaced by RAD51, leading to strand invasion and ensuing HR processes. Gap -- how CtIP and early HR events are regulated, ho...

Note for: The Notch inhibitor cowanin accelerates nicastrin degradation (doi: 10.1038/s41598-018-23698-4) Notch alteration contributes to carcinogenesis. Therefore, it could be used as the target to treat the cancer. Using cell-based system to screen compound from Garcinia speciosa. 1/12 was found to inhibit notch signaling pw. HES1 and HES5 are the targets. Cowanin decreases HES1 and HES5 protein level. Cytotoxic to leukemic HPB-ALL. Notch signaling - many fundamental process; 1.proliferation 2.stem cell maintenance 3.differentiation (well just like wnt signaling pw) It is important for neuronal diff. It has been regulated through hairy and enhancer of split 1 ( HES1 ), HES5 and HES related ( HESR/HEY ) family genes. Aberration in Notch signaling participates in both multiple hematologic and solid malignancies. Notch signaling is activated by interaction between the ligand-expressing cell and the signal-receiving cell. Various Notch inhibitors; ...

Note: Mutant cells defective in DNA repair pathways provide a sensitive high-throughput assay for genotoxicity DNA repair during replication (S-phase) 1. TLS 2. HR 3. FA DNA repair throughout cell cycle; 1. base excision 2. nucleotide excision 3. NHEJ In this paper, the panel that they used; 1. DNA damage checkpoint - ATM 2. HR - Rad54, XRCC3, and UBC13 3. NHEJ - Ku70 4. ICL - FANCC 5. TLS - Rev3 6. NER - XPA and XPG 7. BER - DNA pol-beta My understanding in this paper - they relied on one particular lesion will be majorly used by one particular pw (how much fold should be different then bc DNA repair has the redundancy?). Good points for DT40 again (in year 2010) -  1.High targeted integration 2.Stable karyotype/phenotype even for the long subculture 3.Short doubling time Still, it is chicken - some genes could not be conducted though DNA repair pws have been said to be conserved throughout evolution. 1. Genetic manipulation in mammalian cells - diffi...