Matches in SemOpenAlex for { <https://semopenalex.org/work/W2145367045> ?p ?o ?g. }
- W2145367045 abstract "A remarkable correspondence exists between the cytogenetic locations of the known fragile sites and frequently reported sites of hypermethylation. The best-known features of fragile sites are sequence motifs that are prone to the spontaneous formation of a non-B DNA structure. These facts, coupled with the known enzymological specificities of DNA methyltransferase 1 (DNMT1), the ATP-dependent and actin-dependent helicases, and the ten-eleven translocation (TET) dioxygenases, suggest that these enzymes are involved in an epigenetic cycle that maintains the unmethylated state at these sites by resolving non-B structure, preventing both the sequestration of DNA methyltransferases (DNMTs) and hypermethylation in normal cells.The innate tendency of DNA sequences present at fragile sites to form non-B DNA structures results in de novo methylation of DNA at these sites that is held in check in normal cells by the action of ATP-dependent and actin-dependent helicases coupled with the action of TET dioxygenases. This constitutes a previously unrecognized epigenetic repair cycle in which spontaneously forming non-B DNA structures formed at fragile sites are methylated by DNMTs as they are removed by the action of ATP-dependent and actin-dependent helicases, with the resulting nascent methylation rendered non-transmissible by TET dioxygenases.A strong prediction of the hypothesis is that knockdown of ATP-dependent and actin-dependent helicases will result in enhanced bisulfite sensitivity and hypermethylation at non-B structures in multiple fragile sites coupled with global hypomethylation.A key implication of the hypothesis is that helicases, like the lymphoid-specific helicase and alpha thalassemia/mental retardation syndrome X-linked helicase, passively promote accurate maintenance of DNA methylation by preventing the sequestration of DNMTs at sites of unrepaired non-B DNA structure. When helicase action is blocked due to mutation or downregulation of the respective genes, DNMTs stall at unrepaired non-B structures in fragile sites after methylating them and are unable to methylate other sites in the genome, resulting in hypermethylation at non-B DNA-forming sites, along with hypomethylation elsewhere." @default.
- W2145367045 created "2016-06-24" @default.
- W2145367045 creator A5067251348 @default.
- W2145367045 date "2013-09-30" @default.
- W2145367045 modified "2023-09-26" @default.
- W2145367045 title "Maintaining the unmethylated state" @default.
- W2145367045 cites W1504197144 @default.
- W2145367045 cites W1511523018 @default.
- W2145367045 cites W1550720320 @default.
- W2145367045 cites W1652583010 @default.
- W2145367045 cites W1838266191 @default.
- W2145367045 cites W1963860688 @default.
- W2145367045 cites W1966010051 @default.
- W2145367045 cites W1966135244 @default.
- W2145367045 cites W1966971933 @default.
- W2145367045 cites W1967826363 @default.
- W2145367045 cites W1968391853 @default.
- W2145367045 cites W1970224079 @default.
- W2145367045 cites W1975279481 @default.
- W2145367045 cites W1975621410 @default.
- W2145367045 cites W1976898219 @default.
- W2145367045 cites W1981118438 @default.
- W2145367045 cites W1981463058 @default.
- W2145367045 cites W1983127291 @default.
- W2145367045 cites W1985898834 @default.
- W2145367045 cites W1986566899 @default.
- W2145367045 cites W1993243592 @default.
- W2145367045 cites W1993981510 @default.
- W2145367045 cites W1994473465 @default.
- W2145367045 cites W1996132411 @default.
- W2145367045 cites W1999628666 @default.
- W2145367045 cites W1999791224 @default.
- W2145367045 cites W2001835861 @default.
- W2145367045 cites W2006643590 @default.
- W2145367045 cites W2013143444 @default.
- W2145367045 cites W2013659231 @default.
- W2145367045 cites W2013698368 @default.
- W2145367045 cites W2014607365 @default.
- W2145367045 cites W2014907331 @default.
- W2145367045 cites W2019551631 @default.
- W2145367045 cites W2019904951 @default.
- W2145367045 cites W2025133427 @default.
- W2145367045 cites W2027178459 @default.
- W2145367045 cites W2028238099 @default.
- W2145367045 cites W2028289669 @default.
- W2145367045 cites W2029575827 @default.
- W2145367045 cites W2031363251 @default.
- W2145367045 cites W2038756976 @default.
- W2145367045 cites W2039633981 @default.
- W2145367045 cites W2043500008 @default.
- W2145367045 cites W2045416709 @default.
- W2145367045 cites W2046812959 @default.
- W2145367045 cites W2046981983 @default.
- W2145367045 cites W2051013729 @default.
- W2145367045 cites W2054823635 @default.
- W2145367045 cites W2055230228 @default.
- W2145367045 cites W2062529316 @default.
- W2145367045 cites W2063858714 @default.
- W2145367045 cites W2068990869 @default.
- W2145367045 cites W2070484728 @default.
- W2145367045 cites W2072595668 @default.
- W2145367045 cites W2073200351 @default.
- W2145367045 cites W2073799618 @default.
- W2145367045 cites W2075520328 @default.
- W2145367045 cites W2076127482 @default.
- W2145367045 cites W2077341010 @default.
- W2145367045 cites W2079909703 @default.
- W2145367045 cites W2081414296 @default.
- W2145367045 cites W2081869203 @default.
- W2145367045 cites W2083423525 @default.
- W2145367045 cites W2083632891 @default.
- W2145367045 cites W2085617522 @default.
- W2145367045 cites W2090205848 @default.
- W2145367045 cites W2090450153 @default.
- W2145367045 cites W2092167212 @default.
- W2145367045 cites W2095329435 @default.
- W2145367045 cites W2102676660 @default.
- W2145367045 cites W2102902836 @default.
- W2145367045 cites W2103909453 @default.
- W2145367045 cites W2105333044 @default.
- W2145367045 cites W2107972234 @default.
- W2145367045 cites W2112253005 @default.
- W2145367045 cites W2113437172 @default.
- W2145367045 cites W2114382972 @default.
- W2145367045 cites W2120573925 @default.
- W2145367045 cites W2121082106 @default.
- W2145367045 cites W2121752589 @default.
- W2145367045 cites W2124007239 @default.
- W2145367045 cites W2124043981 @default.
- W2145367045 cites W2125271746 @default.
- W2145367045 cites W2126731001 @default.
- W2145367045 cites W2128077939 @default.
- W2145367045 cites W2129354442 @default.
- W2145367045 cites W2131042290 @default.
- W2145367045 cites W2132070326 @default.
- W2145367045 cites W2134288198 @default.
- W2145367045 cites W2135733051 @default.
- W2145367045 cites W2136905998 @default.
- W2145367045 cites W2139059476 @default.
- W2145367045 cites W2139885759 @default.