Possible association of BLM in decreasing DNA double strand breaks during DNA replication

Citation
Ws. Wang et al., Possible association of BLM in decreasing DNA double strand breaks during DNA replication, EMBO J, 19(13), 2000, pp. 3428-3435
Citations number
47
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
EMBO JOURNAL
ISSN journal
0261-4189 → ACNP
Volume
19
Issue
13
Year of publication
2000
Pages
3428 - 3435
Database
ISI
SICI code
0261-4189(20000703)19:13<3428:PAOBID>2.0.ZU;2-B
Abstract
Bloom's syndrome (BS) is a rare genetic disorder and the cells from BS pati ents show genomic instability and an increased level of sister chromatid ex change (SCE). We generated BLM-/- and BLM-/-/RAD54(-/-) DT40 cells from the chicken B-lymphocyte line DT40. The BLM-/- DT40 cells showed higher sensit ivity to methyl methanesulfonate and elevated levels of SCE as expected. Th e targeted integration frequency was also increased remarkably in BLM-/- ce lls. The SCE frequency increase in BLM-/- cells was considerably reduced an d the enhanced targeted integration observed in BLM-/- cells was almost com pletely abolished in BLM-/-/RAD54(-/-) cells, indicating that a large porti on of the SCE in BLM-/- cells occurs via homologous recombination, and homo logous recombination events increase with the defect of BLM function. The B LM-/-/RAD54(-/-) cells showed a slow growth phenotype and an increased inci dence of chromosome-type breaks/gaps while each single mutant showed relati vely small numbers of chromosome-type breaks/ gaps.