DNA ???????? The consequence of DNA repair deficiencies

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DNA ???????? The consequence of DNA
repair deficiencies
??? ???
2
????

• Photosynthesis ????
• Ultraviolet ???
• Xeroderma pigmentosum ??????
• Nucleotide excision repair ???????
• Cockayne syndrome ??????
• Neurological dysfunction ??????
• Demyelination ???
• Transcription ??
• Nervous systerm ????

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• Basal cell carcinoma ?????
• Squamous cell carcinoma ?????
• Malignant melanoma ??????
• Colon cancer ???
• Mismatch repair ????
• Tumor ??
• Radon ?
• Radioactive isotope ??????
• Disintegration of uranium ???

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???????

• ????????????,????????????????,?????????????????
  ????,??????????
• ???????????????????????????????????????????,??????
  ,???????????????10?(?????)??????????????,????????,
  ?????????

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???????,??????,???????????????????,???????????????
????,???,????????????????????3?

• (1)?????,?????????(?13),????????
• (2)???????,?????????,????????,???50????,????????
  ??????????
• (3)????????,???????,??????DNA?????
  ,??????,????????

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??????
xeroderma pigmentosum
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??????(XP)????????????????????????,???????????????
??????????????????DNA????????????????
50???XP???De Sacchione?????,???????????,????,??
????????,??????????,??????????????????????????????
?? ???????????????,??????????,????????????????????
(???????????)?????????????????????????????????????
?????????????????????????????????????????,???????3
0???????,???1120?????????????????????????????????
???? XP?7????(A-G),6?????,?XPA?ERCC-3?XPC?ERCC-2?E
RCC-4?ERCC-5?
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????

• ????????DNA?,??????260nm????????,??????????,???
  ?????DNA????.????????DNA,???????,?????????,???????
  ???????????????????????????(TT ) ??????????
  (CC)?????????????(CT)?

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??????????????????,?DNA??????,???????DNA??????????
?????DNA???,??????DNA?????,?????????????????????
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• ??????DNA????????TF?H???
• ??xPB?xPD??TF?H?
• XP???XPB?XPD ? ?????????????????????DNA???????TF
  ?H ? ??

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??

• ???????????????????

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?1 ?,10?,???4????????,89????????????,????????????
???????,???????,????,?????????,????,?????,3???????
?????????????????????????,????????,??????????,????
???????????????????,?????????????,????????????????
?,??????????,????????5????????,?????????????,??
??????????????,???????????????????,?????,???????
,????2?3??,3?4????????????????6cm,???3cm???,??,??
?????????????????????,??????????????????????,???
???,??????????????????????????,???????????????????
???????????????????????????????,??????????????????
?????????,?????????
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?????????125g/L,???5.351012/L????11.4109/L?????
?0.7?????0.28?????0.02???()????()/??????()/?
????03/???????8.5mmol/L???ALT32U?TTT
12UX????????,???????????????,R??????T???,?????
??????????????????????????????????????????,???
???,????????,??????????,??????????,?????????????

• ???????????????

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?2 ?,6?,?1??,??????????????????????????X?????????
??????????,????????,?????????,??????????????????
??,P???,?????,PR????????????????????????????????
??????????????????2.2???

• ???????????????

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???????????????????,?????E??????????????1?????3?
??2??????????????????,????????,?????,???????,?????
?????????????????????????????????,?????,?????,??
???,????????

• ??
• ??????
• ?????1?2??????????

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???????

• ?????

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• Darkly pigmented regions of the skin are evident
  in this boy with xeroderma pigmentosum. The area
  of skin below the chin, which is protected from
  the sun, is relatively devoid of the lesions.

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XP???

• ??XP????????????????????DNA?????????????(????????,
  ????????????????)?????UV???????????????????????
• ?????????60???????????,??????????? ?????????

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(No Transcript)
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• ???????????
• ??,????????,?????????
• ????
• ????????,
• ????????????????????4???
• ???
• ??????,???????????????????
• ?????????????????????

????
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??

• ??????DNA????????????????
• ???????????
• ??????????
• ??????????????
• ??????????????

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??????DNA????????????????

• ????,????????,?????????????????A??????????????????
  ????????????,???????????????????PCR-DNA???????????
  ????????????,????????????A????????????????????????
  ?????????????,????????????????????DNA??????,??????
  ??????????????????,?????????????

??
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????????????????????

• ??????????????????????????????????,???????????????
  ?????????????????????????????????????????????

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• ???????????????,2002?,?????????????????????????
  ??????,????????????????
• ???????????????????????????????????????????????
  ???,???????????????????,??????????????????????

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• ??????????????????????????????????????????????????
  ???????????,??????????????????????????????????????
  ???????????,??????????????????????????????????,???
  ????????????????
• ?????????????????????????????????,????????????????
  ????????,?????????????2004?????,?????????????????

??
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??????????????

• ??1970?Cleaver?????,??????????????????????????????
  ?(nucleotide excision repair,NER)???
• 1985?,???NER????????????????RAD3???
• 1987?,Sung??????Rad3p????????DNA?????????
• 1990?,???????????????xPD,??????NER???RAD3?????????
  ?????????NER???????????????????
• ???????1993?,????xPBp?xPDp???????RNA?????TF?H?????
  ??????????xPBp?xPDp?????????(RAD3?RAD25)
  ??????????,????????????????????????

??
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??????????????

• ???????????????????????????????????,??????????????
  ??????,??????????????????
• ????????????????????????????????????????????????
  ????????????????????????????,????????????????,????
  ???????????????????????
• ?????,????????????????????????????????????????????
  ???????????,???????????????????????,??????????????
  ?

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??????(CS)
??-?????-????? ????????
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CS????????,??????,????????????????????????????,
?????????,??????????,?????????????(???????,????,??
???)? ??CS???????????,??????????????????????????
??????????
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????

• CS???CSA?CSB ? ?????????????????????DNA???????TF?H
  ? ??
• CS????????????????

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??CS?XP???????,?CS?? ????????????
???????????????? ????
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• ?????DNA??????,?????
• ??????????????,?????
• ??????????
• ????XP?????????XP????????????,?CS??????????CS????
  ?????????