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

被引：124

作者：

Wang, WS

Seki, M

Narita, Y

Sonoda, E

Takeda, S

Yamada, K

Masuko, T

Katada, T

Enomoto, T ^{[1
]}

机构：

[1] Tohoku Univ, Grad Sch Pharmaceut Sci, Mol Cell Biol Lab, Aoba Ku, Sendai, Miyagi 9808578, Japan

[2] Kyoto Univ, Fac Med, Kyoto 6068315, Japan

[3] Kyoto Univ, Bayer Chair Dept Mol Immunol & Allergol, Kyoto 6068315, Japan

[4] Natl Inst Hlth & Nutr, Div Geriatr Hlth Sci, Tokyo 1628636, Japan

[5] Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Physiol Chem, Tokyo 1130033, Japan

来源：

EMBO JOURNAL | 2000年 / 19卷 / 13期

关键词：

BLM; chromosome-type breaks; HR; RAD54; SCE;

D O I：

10.1093/emboj/19.13.3428

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Bloom's syndrome (BS) is a rare genetic disorder and the cells from BS patients show genomic instability and an increased level of sister chromatid exchange (SCE). We generated BLM-/- and BLM-/-/RAD54(-/-) DT40 cells from the chicken B-lymphocyte line DT40. The BLM-/- DT40 cells showed higher sensitivity to methyl methanesulfonate and elevated levels of SCE as expected. The targeted integration frequency was also increased remarkably in BLM-/- cells. The SCE frequency increase in BLM-/- cells was considerably reduced and the enhanced targeted integration observed in BLM-/- cells was almost completely abolished in BLM-/-/RAD54(-/-) cells, indicating that a large portion of the SCE in BLM-/- cells occurs via homologous recombination, and homologous recombination events increase with the defect of BLM function. The BLM-/-/RAD54(-/-) cells showed a slow growth phenotype and an increased incidence of chromosome-type breaks/gaps while each single mutant showed relatively small numbers of chromosome-type breaks/ gaps.

引用

页码：3428 / 3435

页数：8

共 47 条

[1] Binding specificity determines polarity of DNA unwinding by the Sgs1 protein of S-cerevisiae [J].