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ID 14206
file
creator
Nakazaki, Tomofumi
Akamatsu, Yufuko
Watanabe, Kikuo
Tomita, Kazunori
Lindsay, Howard D.
Shinagawa, Hideo
Iwasaki, Hiroshi
subject
MRN
nbs1
methyl methanesulfonate
genetic disease
Nijmegen breakage syndrome
NDC
Physics
abstract
The human MRN complex is a multisubunit nuclease that is composed of Mre11, Rad50, and Nbs1 and is involved in homologous recombination and DNA damage checkpoints. Mutations of the MRN genes cause genetic disorders such as Nijmegen breakage syndrome. Here we identified a Schizosaccharomyces pombe nbs1+ homologue by screening for mutants with mutations that caused methyl methanesulfonate (MMS) sensitivity and were synthetically lethal with the rad2△ mutation. Nbs1 physically interacts with the C-terminal half of Rad32, the Schizosaccharomyces pombe Mre11 homologue, in a yeast two-hybrid assay. nbs1 mutants showed sensitivities to γ-rays, UV, MMS, and hydroxyurea and displayed telomere shortening similar to the characteristics of rad32 and rad50 mutants. nbs1, rad32, and rad50 mutant cells were elongated and exhibited abnormal nuclear morphology. These findings indicate that S. pombe Nbs1 forms a complex with Rad32-Rad50 and is required for homologous recombination repair, telomere length regulation, and the maintenance of chromatin structure. Amino acid sequence features and some characteristics of the DNA repair function suggest that the S. pombe Rad32-Rad50-Nbs1 complex has functional similarity to the corresponding MRN complexes of higher eukaryotes. Therefore, S. pombe Nbs1 will provide an additional model system for studying the molecular function of the MRN complex associated with genetic diseases.
journal title
Molecular and cellular biology
volume
Volume 23
start page
6553
end page
6563
date of issued
2003-09
publisher
American Society for Microbiology
issn
0270-7306
language
eng
nii type
Journal Article
HU type
Journal Articles
DCMI type
text
format
application/pdf
text version
author
rights
Copyright (c) 2003 American Society for Microbiology
relation is version of URL
http://dx.doi.org/10.1128/MCB.23.18.6553-6563.2003
department
Graduate School of Advanced Sciences of Matter