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Note: Small-Molecule Inhibitors Targeting DNA Repair and DNA Repair Deficiency in Research and Cancer Therapy (doi: 10.1016/j.chembiol.2017.08.027) Process that maintain genome integrity in normal cells - it will help cancer to develop resistance to radiation and DNA-damaging chemotherapeutics. New target; RAD51 recombinase, RAD52, and MRE11 nuclease, WRN DNA helicase. Synthetic lethality - two individual mutations but when combined  resulting in lethal phenotype. Hartwell, is the first guy who initiated the synthetic lethality with the cancer baring the DNA-repair proteins defect. Also, cancer that addict to particular DNA repair mechanism. Therefore, the target for synthetic lethality is that finding the protein that the cancer cell relied on for viability (but less important in normal cell) and inhibit theirs function. Synthetic lethality; two types 1.between-pathway (each backup for each other) 2.In-pw synthetic lethality, mutation either way of revers...

Note for: The DNA-damage response in human biology and disease (doi: 10.1038/nature08467) DNA damage response detection is very essential process in living organism to maintain the right balance between the diversity (fit well to the external) and the disease (unfit to the external). 1.DNA lesion can occur either both physiological and pathological condition. 2.physilogical lesion -- DNA mismatch//break by topo-i and topo-ii Damage occurs through: 1.oxidative respiration 2.redox-cycling (membrane of mitochondria) 3.Fenton reaction (redox reaction catalyzed by Fe) 4.NOS and ROS produce during inflammation and infection DNA double-strand break is rarely found but very toxic once it is generated. DNA damage responses differentially occur depending on the classes of DNA lesions. The process could be separated as follow; 1.damage or stalled replication/transcription 2.detection by sensors 3.recruitment of mediators 4.amplifying the signal 5.transduc...