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Summary of Research Projects (Supports in 2005
Fiscal Year)
| Subjects |
Dynamic regulation of SMC-like RecN protein in response
to DNA double-strand breaks in Escherichia coli. |
Representative
researcher |
Osaka University Takashi HISHIDA
|
| DNA double-strand breaks (DSBs) are major
threats to the genomic integrity of cells. These result from exogenous
and endogenous agents such as ionizing radiation and chemical mutagen and
from endogenously produced radicals. Therefore, the repair of DSBs is important
for cell survival and for maintaining the integrity of the genome. Escherichia
coli recN is a member of the structural maintenance of chromosomes
(SMC) family and is required for DNA double-strand break repair. This study
shows that RecN protein has a short half-life and its degradation is dependent
on the cytoplasmic protease ClpXP and a degradation signal at the C-terminus
of RecN. In cells with DNA DSBs, GFP-RecN localized in discrete foci on
nucleoids and also formed visible aggregates in the cytoplasm, both of
which disappeared rapidly in wild-type cells when DSBs were repaired. In
contrast, in ∆clpX cells, RecN aggregates persisted in the
cytoplasm after release from DNA damage. Furthermore, analysis of cells
experiencing chronic DNA damage revealed that proteolytic removal of RecN
aggregates by ClpXP was important for cell viability. These data demonstrate
that ClpXP is critical component of the cellular clearance of toxic RecN
aggregates from the cell, and therefore plays an important role in DNA
damage tolerance. |
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