Delayed DNA maturation, a possible cause of the elevated sister-chromatid exchange in Bloom's syndrome.
AffiliationPaterson Laboratories, Christie Hospital, Manchester M20 9BX UK
MetadataShow full item record
AbstractDifferences in behaviour between the 5-bromodeoxyuridine (BrdU)-substituted template strands in Bloom's syndrome (BS) and normal human fibroblasts have been investigated in order to elucidate the mechanism responsible for the elevated baseline sister-chromatid exchange (SCE) frequency in BS. Alkaline sucrose gradient analysis of the normal and BrdU-substituted DNA strands showed the former to be of higher mol. wt. and of mature size while the latter were of lower molecular size, resulting from breaks introduced during the repair of the BrdU with no differences discernible between BS and normal cells. The rates of removal of BrdU were similar in BS and normal cells, which indicates that the increased SCE level in BS is not due to different rates of repair of the BrdU. The maturation of newly synthesized DNA on a normal template is delayed in BS cells compared with normal cells although it is complete at 18 h, the time it is acting as a template for DNA synthesis. In the presence of a BrdU-substituted template the maturation although further delayed is complete in normal cells by 12 h but in BS cells is not complete even by 30 h, when the newly synthesized strand, due to cell cycle delay produced by the incorporation of BrdU, becomes a template in the next round of DNA synthesis. It is suggested that a similar delay in maturation probably occurs when a new strand containing BrdU is synthesized on a normal template in BS cells. When these strands act as a template they will contain two types of breaks--those due to BrdU repair and those due to delayed maturation. The latter will be responsible for the elevated SCEs in BS cells as the DNA replication forks move through them in a manner similar to that previously reported. The possible implications of differential delays in cell proliferation in BrdU, rates of BrdU removal and extent of DNA maturation in this syndrome are discussed.
CitationDelayed DNA maturation, a possible cause of the elevated sister-chromatid exchange in Bloom's syndrome. 1986, 7 (1):53-7 Carcinogenesis
- Bromodeoxyuridine does not contribute to sister chromatid exchange events in normal or Bloom syndrome cells.
- Authors: van Wietmarschen N, Lansdorp PM
- Issue date: 2016 Aug 19
- 5-Bromodeoxyuridine-dependent increase in sister chromatid exchange formation in Bloom's syndrome is associated with reduction in topoisomerase II activity.
- Authors: Heartlein MW, Tsuji H, Latt SA
- Issue date: 1987 Mar
- Inhibition of bromodeoxyuridine-associated sister chromatid exchanges in Bloom's syndrome cells with cycloheximide.
- Authors: Shiraishi Y, Yosida TH, Sandberg AA
- Issue date: 1985 May