title: Functional interactions between BLM and XRCC3 in the cell.
abstract: 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.
authors.affiliation: Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Science, Tohoku University, Sendai 980-8578, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Otsuki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Seki
authors.forename: Eri
authors.initials: E
authors.lastname: Inoue
authors.forename: Akari
authors.initials: A
authors.lastname: Yoshimura
authors.forename: Genta
authors.initials: G
authors.lastname: Kato
authors.forename: Saki
authors.initials: S
authors.lastname: Yamanouchi
authors.forename: Yoh-ichi
authors.initials: Y
authors.lastname: Kawabe
authors.forename: Shusuke
authors.initials: S
authors.lastname: Tada
authors.forename: Akira
authors.initials: A
authors.lastname: Shinohara
authors.forename: Jun-ichiro
authors.initials: J
authors.lastname: Komura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ono
authors.forename: Shunichi
authors.initials: S
authors.lastname: Takeda
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Ishii
authors.forename: Takemi
authors.initials: T
authors.lastname: Enomoto
mesh_terms: 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
chemical_list: 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