Random Records

Note: Mechanisms of DNA double-strand break repair and their potential to induce chromosomal aberrations_2000 Doi: 10.1093/mutage/15.4.289 Theory of cancer formation Breakage and reunion theory Exchange theory Molecular theory Initial lesion -- chemical and physical-DNA damaging agents Artificially induced DSB IR Endonuclease Cellular (spontaneous) sources of DSB Can occur in any stage of cell cycle Briefly summarize the main causes of spontaneous DSB Topoisomerases Topo-I -- generates SSB Topo-II -- generate DSB Replication Prevalent source of DSB -- DNA replication Cell estimates to suffer ~ 10 DSB/cell cycle (estimate from spontaneous sister chromatid exchange) Meiosis V(D)J recombination Other recombinant process Transposable elements Fragile sites Extended micro- and minisatellite sequences -- potential source of DSB in mammalian genome At this time of writing (2000) -- the instability of this fragile site is not well-understood DSB as a results of excision repair Considering on t...

Note: Gamma-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin (doi: 10.1093/nar/gkn550) Three PI3KK can phosphorylate H2Ax; ATM, ATR and DNA-PK – each requires partner to recognize the break differently. MRN-ATM (heterochromatin region, S/G2-phase), ATRIP-ATR (stalled replication fork or bulk-damage entering to S-phase) and KU70/80-DNA-PK (occur throughout cell cycle). Scoring gH2Ax requires attention since it is not solely represented DSB. Remaining of gH2Ax foci does not mean the DSB has not been fixed. It may remain there to signal the HR to do more additional repair after seal with NHEJ, or the phosphatase system might be malfunction. The further condensation of the 30nm fiber as well as higher levels of chromatin condensation, which culminate with the 10 000-fold compaction of the stretched DNA fiber in the 700nm metaphase chromosomes, are less well understood, but are facilitated by the linker histone H1 and condensins. By ...

Note for: ATM, ATR, and DNA-PK: The Trinity at the Heart of the DNA Damage Response doi: 10.1016/j.molcel.2017.05.015 Freaking complicated and so many gaps in the research as well as the available tool to elaborate precise mechanism. In general, a cell’s DNA damage response (DDR) involves DNA lesion recognition, followed by initiation of a cellular signaling cascade to promote DNA repair, which can be aided by a pause in cell-cycle progression (checkpoint activation). In concert with such events, cells mediate other responses, including modulation of chromatin structure and transcription, both at sites of DNA damage and more globally. DNA damage permanently exit the cell cycle (senescence) or undergo programmed cell death (apoptosis), presumably to mitigate the propagation of potentially mutated cells leading to cancer or other age-related pathologies. DNA lesions also serve as intermediates in certain biological processes, such as DNA demethylation, meiotic recombina...

Current research: Our current research group is focusing on the DNA repair pathways, especially, DNA double-strand break repairs. DNA repair is a vital mechanism and its malfunction can cause cancer. In contrast, the cancer cells also exploit the repair mechanism to facilitate tumor growth. Since the DNA repair mechanism is complex, thus, there are numbers of genes/proteins which their precise role in carcinogenesis is elusive. To explore the function of novel DNA double-strand break repair genes/proteins in carcinogenesis, our research group have used the reverse genetic approach to understand the mechanism. Because the targeted-therapy in the DNA repair pathway is very expensive and limited, we would like to search for the new lead compounds which could be developed in our country. We are now setting up the biosensor based on DNA double-strand break repair and using the high throughput screening technology (HST) to find the candidate compounds that are from local endophytic extract...