Functional interactions between BLM and XRCC3 in the cell.
Bloom's syndrome (BS), which is caused by mutations in the BLM gene, is characterized by a predisposition to a wide variety of cancers. BS cells exhibit elevated frequencies of sister chromatid exchanges (SCEs), interchanges between homologous chromosomes (mitotic chiasmata), and sensitivity to several DNA-damaging agents. To address the mechanism that confers these phenotypes in BS cells, we characterize a series of double and triple mutants with mutations in BLM and in other genes involved in repair pathways. We found that XRCC3 activity generates substrates that cause the elevated SCE in blm cells and that BLM with DNA topoisomerase IIIalpha suppresses the formation of SCE. In addition, XRCC3 activity also generates the ultraviolet (UV)- and methyl methanesulfonate (MMS)-induced mitotic chiasmata. Moreover, disruption of XRCC3 suppresses MMS and UV sensitivity and the MMS- and UV-induced chromosomal aberrations of blm cells, indicating that BLM acts downstream of XRCC3.
Otsuki
Makoto
M
Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Science, Tohoku University, Sendai 980-8578, Japan.
Seki
Masayuki
M
Inoue
Eri
E
Yoshimura
Akari
A
Kato
Genta
G
Yamanouchi
Saki
S
Kawabe
Yoh-ichi
Y
Tada
Shusuke
S
Shinohara
Akira
A
Komura
Jun-ichiro
J
Ono
Tetsuya
T
Takeda
Shunichi
S
Ishii
Yutaka
Y
Enomoto
Takemi
T
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001816:Bloom Syndrome / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002645:Chickens; D002869:Chromosome Aberrations; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D053484:RecQ Helicases; D011995:Recombination, Genetic; D012854:Sister Chromatid Exchange; D014466:Ultraviolet Rays
D004268:DNA-Binding Proteins; C110901:X-ray repair cross complementing protein 3; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases