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Note for: DNA double-strand break repair pathway choice: a chromatin based decision? (doi: 10.1080/19491034.2015.1010946) The choice between these pathways is a critical, yet not completely understood, aspect of DSB repair. DSBs induced across the genome are not repaired by the same pathway. DSBs induced in active genes, naturally enriched in the trimethyl form of histone H3 lysine 36 (H3K36me3), are channeled to repair by HR, in a manner depending on SETD2, the major H3K36 trimethyltransferase. This “decision making” function of preexisting chromatin structure in DSB repair could connect the repair pathway used to the type and function of the damaged region, not only contributing to genome stability but also to its diversity. Importantly failure or misuse of each of these DSB repair pathways can trigger very different consequences on the genome. NHEJ is the primary cause of translocations and dysfunctional telomeres fusion. HR pathways can be entirely conservative when the...

Note: Endogenous DNA Double-Strand Breaks during DNA Transactions: Emerging Insights and Methods for Genome-Wide Profiling (doi: 10.3390/genes9120632) Additionally, chromatin looping involved in 3D genome organization and gene regulation is increasingly recognized as a possible contributor to DSB events. This review; 1.mechanisms of endogenous DSB formation 2.genome-wide profiling of DSB Future direction on this field -- genome-wide DSB formation and repair. DSBs can trigger cell death or give rise to structural genomic rearrangements associated with carcinogenesis and other diseases. The frequency of DSBs is estimated to be 10–50 events per cell per day. in healthy individuals the majority of DSBs is thought to originate from within the nucleus, where DSBs form during fundamental processes such as DNA replication, meiosis, antibody diversification, gene transcription, and—although indirectly—cellular metabolism. DNA transactions—especially during DNA rep...

Note: Transcription-Coupled DNA Double-Strand Break Repair: Active Genes Need Special Care (doi: 10.1371/journal.pgen.1006895) Specific loci on eukaryotic chromosomes are inherently susceptible to breakage. Transcriptionally active loci are particularly fragile and that a specific DNA damage response is activated and dedicated to their repair. Review on – crosstalk between transcription and double-strand break repair, from intrinsic fragility of genes to the mechanisms that restore the integrity of damaged transcription units. DNA double helix is irregular: it can form non-canonical structures such as R-loops (three stranded structures composed of RNA:DNA hybrids and single-stranded DNA), hairpins, G-quadruplex (G4), and underwound or over-twisted DNA helices that are further translated into negative and positive supercoiling. The transcription, replication, and repair machineries must cope with this great variety of secondary and tertiary structures if they are to accurat...

PTM for Histone; 1. acetylation (Lys) 2. ubiquitination (Lys) 3. phosphorylation (Ser) H2Ax when phosphorylate --> gammaH2Ax! nucleosome = histone (H2A,H2B,H3,H4) + 147 bp DNA wrapping around 8 octa-histone and being locked with H1 (shown in my drawing) For H2A subdivided to 3; H2A1-H2A2 (balance from the other two) H2Ax (2-25%) H2Az (10%) Ref; DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139 ( J Biol Chem.  1998 Mar 6;273(10):5858-68.)