Excess thymidine induces folate sensitve fragile sites

Abstract

Folate sensitive fragile sites on human chromosomes have been found to be inducible in cultured lymphocytes by high levels of thymidine but not by high levels of BrdU. The biochemical interpretation of events leading to fragile site expression has been revised since it is now clear that low levels of either thymidylate or deoxycytidine triphosphate will result in this phenomenon. A model for the DNA at a fragile site, composed of alternating repeating polypurine/polypyrimidine sequences is proposed.

Interstitial telomeres are hotspots for illegitimate recombination with DNA molecules injected into the macronucleus of Paramecium primaurelia.

“…Sen and Gilbert in 1988, have shown that singlestranded oligonucleotides with sequences characteristic of the guanine-rich strand in the immunoglobulin heavy chain switch region can self-associate to form four-stranded structures of the G4 type (Sundquist and Klug, 1989;Williamson et al, 1989). Moreover, fragile sites prone to recombination are frequently monotonous stretches of either cytosine and thymine or guanine and thymine residues on one strand (Sutherland et al, 1985;Nussbaum et al, 1986).…”

Report of the committee on chromosome rearrangements in neoplasia and on fragile sites

“…Rare fragile sites T Folate sensitive fragile sites These are induced in lymphocyte chromosomes by low folic acid and thymidine concentrations in the culture medium (Sutherland, 1979a), by inhibitors of folate metabolism such as methotrexate (Sutherland, 1979a;Mattei et al, 1981), by specific inhibition of thymidylate synthetase by FUdR (Glover, 1981;Tommerup et al, 1981), or FCdR (Jacky and Sutherland, 1981), and by high concentrations of thymidine (Sutherland et al, 1985b).…”

Segregation analysis of rare autosomal folate sensitive fragile sites

“…The terms used to denote these sites a¡e "constitutive" (Daniel et al, l9g4;Yunis and Soreng, 1984) and "common" (Glover et al, 1984;Suthe¡land and Hecht 1985b), as well as ''hoçoints" (Zhou et al, 1984) and aurosomal "lesions,' (Sutherland, 1983 (Hecht, 1988) (Iable I and Table tr (Hecht, 1988 (Sutherland et aL, 1985c). Sutherland et al (1985c) (Sutherland, 1979b This increasing effect was highly significanr for sires at 2q13,20p11, XqZ7, bur nor for those 10q25, 11q13, 16p12 and 12q13 (Sutherland et al, 1981). The rare of folate uptake by cells was inversely proportion to pH and higher inuacellular levels of folate in a steady state situation have been found at lower pH of the culture medium (Branda et al, 1982 (Sutherland and Hinton, 1981 Jacky et al (1980) when sodium cirrare was used as the hypotonic agent instead of KCl.…”