Download Xeroderma Pigmentosum(XP)

Xeroderma
Pigmentosum(XP)
着色性干皮病
• We owe our lives to light from the sun,which
provides the energy captured during
photosynthesis (光合作用).
• But the sun also emits a constant stream of
ultraviolet rays that ages and mutates the cells of
our skin.
• The hazardous effects of the sun are most
dramatically illustrated by the rare recessive
genetic disorder , Xeroderma Pigmentosum(XP) .
Patients with XP possess a dificient repair system that
cannot remove segments of DNA damaged by
ultraviolet(紫外线) radiation.
• As a result ,person with XP
are extremely sensitive to
sunlight
• Even very limited exposure
to the direct rays of the sun
can produce large numbers
of dark-pigmented spots on
exposed areas of the body
and a greatly elevated risk of
developing disfiguring and
fatal skin cancers.
The mechanism about XP
------nucleotide excision repair deficiency
(核苷酸切除修复缺陷)
• When subjected to
ultraviolet
radiation ,adjacent(相邻
的) pyrimidines(嘧啶) on
a DNA strand have a
tendency to interact with
one another to form a
covalent(共价的) dimer
complex.(example as TT--胸腺嘧啶二具体)
• Once TT is
formed,
ultraviolet radiated
DNA will not be
repaired correctly.
• The replication and
the transcription of
DNA will be
influenced seriously.
• THF II H--- a crucial link between transcription
and DNA repair
• XPB and XPD are two subunits of THF II H
• In persons with XP who carry
specific mutations in the XPD
gene.
• XPD gene encodes a subunit
of the TFII H required for
transcription initiation(起始)
• So, Mutations in XPD could
lead to defect(缺陷) in both
DNA repair and transcription
nucleotide excision repair
How to help XP patients?
• Some help for XP patients may be on the way in the
form of skin creams that contain DNA repair enzymes.
• The enzyme are contained in liposomes(脂质体) that
can apparently penetrate (穿过) the outer layer of the
skin and participate in repair pathways
• XP is a very rare condition ,but colon cancer(结肠
癌) is relatively common.
• It is estimated that up to 15 percent of colon
cancer cases can be attributed to mutations in the
genes that encode the proteins required for
mismatch repair.
• Mutations that cripple the mismatch repair system
inevitably lead to higher mutation rate in other
genes because mistakes made during replication
are not corrected.