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PMID: 17923529 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Functional interactions between BLM and XRCC3 in the cell.

The Journal of cell biology ·Vol. 179 ·No. 1 ·2007-10-08 ·Pages 53-63

Otsuki M, Seki M, Inoue E, Yoshimura A, Kato G, Yamanouchi S, Kawabe Y, Tada S, Shinohara A, Komura J, Ono T, Takeda S, Ishii Y, Enomoto T

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.

MeSH Terms
Adenosine Triphosphatases/genetics,metabolism,physiology Animals Bloom Syndrome/genetics,metabolism Cell Line Chickens Chromosome Aberrations DNA Helicases/genetics,metabolism,physiology DNA Repair/genetics DNA-Binding Proteins/genetics,metabolism,physiology Genetic Predisposition to Disease Humans Mutation RecQ Helicases Recombination, Genetic Sister Chromatid Exchange Ultraviolet Rays
Chemicals
DNA-Binding Proteins X-ray repair cross complementing protein 3 Adenosine Triphosphatases Bloom syndrome protein DNA Helicases RecQ Helicases
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Otsuki Makoto
Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Science, Tohoku University, Sendai 980-8578, Japan.
Seki Masayuki
Inoue Eri
Yoshimura Akari
Kato Genta
Yamanouchi Saki
Kawabe Yoh-ichi
Tada Shusuke
Shinohara Akira
Komura Jun-ichiro
Ono Tetsuya
Takeda Shunichi
Ishii Yutaka
Enomoto Takemi
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200702183
Published
2007-10-08
Pages
53-63
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2064734
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.200702183 PMC Full Text View journal details
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