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

nucleotide excision repair

• 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

How to help XP patients?• Some help for XP patients may be on the way in the f

orm 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.