XPC (基因)

XPC (基因)
已知的結構
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	2A4J、2GGM、2OBH、2RVB
識別號
別名	XPC；, RAD4, XP3, XPCC, p125, xeroderma pigmentosum, complementation group C, XPC complex subunit, DNA damage recognition and repair factor
外部ID	OMIM：613208 MGI：103557 HomoloGene：3401 GeneCards：XPC
相關疾病
	xeroderma pigmentosum group C
基因位置（小鼠）
染色體	小鼠6號染色體
終止	91,492,870 bp
RNA表達模式
	查閱更多表達數據
基因本體
分子功能	• DNA結合; • heteroduplex DNA loop binding; • bubble DNA binding; • single-stranded DNA binding; • damaged DNA binding; • 血漿蛋白結合; • 大分子複合物結合;
細胞組分	• 細胞質; • 細胞膜; • 核質; • XPC complex; • 核仁; • nucleotide-excision repair factor 2 complex; • 細胞核; • 線粒體; • 細胞內膜結合細胞器; • nucleotide-excision repair complex;
生物學過程	• 核苷酸切除修復; • regulation of mitotic cell cycle phase transition; • nucleotide-excision repair, DNA damage recognition; • mitotic intra-S DNA damage checkpoint signaling; • cellular response to DNA damage stimulus; • global genome nucleotide-excision repair; • response to auditory stimulus; • DNA錯配修復; • response to UV-B; • UV-damage excision repair; • DNA修復; • nucleotide-excision repair, preincision complex assembly; • nucleotide-excision repair, DNA duplex unwinding;
	Sources:Amigo / QuickGO
直系同源
	7508
	22591
	ENSG00000154767
	ENSMUSG00000030094
	Q01831
	P51612
	NM_001145769; NM_004628
	NM_009531
	NP_004619; NP_001341655; NP_001341656; NP_001341658; NP_001341659
	NP_033557
	維基數據
檢視/編輯人類	檢視/編輯小鼠

互補組 C 型色素性皮膚病又稱 XPC，是一種人體中由XPC基因編碼的蛋白質。 XPC 參與核苷酸切除修復過程中對大塊 DNA 加合物的識別。 ^[5]它位於3號染色體上^[6]。

功能

該基因編碼核苷酸切除修復（NER）途徑的一個組成部分。 NER通路涉及多種成分，包括着色性干皮病（XP）AG和V、科凱恩綜合徵（CS）A和B、毛髮硫營養不良（TTD）A組等。該成分XPC在全球基因組 NER 的早期步驟，特別是損傷識別、開放複合物形成和修復蛋白複合物形成。 ^[5]

XPC-RAD23B 複合物是全局基因組核苷酸切除修復(GG-NER) 中的初始損傷識別因子。 ^[7] XPC-RAD23B 可識別多種熱力學破壞 DNA 雙鏈體穩定性的損傷，包括 UV 誘導的光產物（環嘧啶二聚體和 6-4 光產物）、環境誘變劑（如苯並[a]芘或各種芳香胺）形成的加合物、某些氧化內源性病變，例如環嘌呤和癌症化療藥物（例如順鉑）形成的加合物。 XPC-RAD23B 的存在是其他核心NER因子的組裝以及體外和體內 NER 途徑進展所必需的。 ^[8]儘管大多數研究都是使用 XPC-RAD23B 進行的，但它是與 centrin-2（鈣調蛋白家族的鈣結合蛋白）三聚體複合物的一部分。 ^[8]

臨床意義

該基因或其他一些 NER 成分的突變會導致色素性干皮病，這是一種罕見的常染色體隱性遺傳疾病，其特徵是對陽光的敏感性增加，並在早期發展為癌症。 ^[5]

癌症

DNA 損傷似乎是癌症的主要原因^[9] ，而 DNA 修復基因的缺陷可能是多種癌症的根源。 ^[10] ^[11]如果DNA修復有缺陷，DNA損傷就會累積。這種過度的 DNA 損傷可能會由於易出錯的跨損傷合成而增加突變。過度的 DNA 損傷還可能增加由於 DNA 修復過程中的錯誤而導致的表觀遺傳改變。 ^[12] ^[13]這種突變和表觀遺傳改變可能會導致癌症。

DNA 修復基因表達的減少（通常由啟動子高甲基化等表觀遺傳改變引起）在癌症中非常常見，並且通常比癌症中 DNA 修復基因的突變缺陷更常見。^{[來源請求]}</link>^{[需要引用]}下表顯示 XPC 表達在膀胱癌和非小細胞肺癌中經常發生表觀遺傳性降低，並且還顯示 XPC 在這些癌症的晚期階段更頻繁地降低。

癌症中 XPC 表達降低的頻率，並分別標明癌症的分期
癌症	頻率	參考號
膀胱癌	50%	^[14]
低度惡性潛能乳頭狀尿路上皮腫瘤	35%	^[14]
低度惡性乳頭狀膀胱癌	42%	^[14]
高級別乳頭狀膀胱癌	65%	^[14]
非小細胞肺癌（NSCLC）	70%	^[15]
非小細胞肺癌 I 期	62%	^[15]
非小細胞肺癌 II-III 期	77%	^[15]

雖然XPC基因啟動子區域的表觀遺傳高甲基化與 XPC 的低表達相關， ^[14] XPC的另一種表觀遺傳抑制模式也可能通過microRNA miR-890 的過度表達而發生。 ^[16]

互動

XPC（基因）已被證明與ABCA1 、 ^[17] CETN2 ^[18]和XPB相互作用。 ^[19]

參考

^ 與XPC (基因)相關的疾病；在維基數據上查看/編輯參考.
^ ^2.0 ^2.1 ^2.2 GRCm38: Ensembl release 89: ENSMUSG00000030094 - Ensembl, May 2017
^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^5.0 ^5.1 ^5.2 Entrez Gene: XPC xeroderma pigmentosum, complementation group C.
^ OMIM Entry - # 278720 - XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP C; XPC. [12 December 2014]. （原始內容存檔於2023-03-07）.
^ Sugasawa K, Ng JM, Masutani C, Iwai S, van der Spek PJ, Eker AP, Hanaoka F, Bootsma D, Hoeijmakers JH. Xeroderma pigmentosum group C protein complex is the initiator of global genome nucleotide excision repair. Mol. Cell. 1998, 2 (2): 223–32. PMID 9734359. doi:10.1016/s1097-2765(00)80132-x .
^ ^8.0 ^8.1 Schärer OD. Nucleotide excision repair in eukaryotes. Cold Spring Harbor Perspectives in Biology. Oct 2013, 5 (10): a012609. PMC 3783044 . PMID 24086042. doi:10.1101/cshperspect.a012609.
^ Kastan MB. DNA damage responses: mechanisms and roles in human disease: 2007 G.H.A. Clowes Memorial Award Lecture. Mol. Cancer Res. 2008, 6 (4): 517–24. PMID 18403632. doi:10.1158/1541-7786.MCR-08-0020 .
^ Harper JW, Elledge SJ. The DNA damage response: ten years after. Mol. Cell. 2007, 28 (5): 739–45. PMID 18082599. doi:10.1016/j.molcel.2007.11.015 .
^ Dietlein F, Reinhardt HC. Molecular pathways: exploiting tumor-specific molecular defects in DNA repair pathways for precision cancer therapy. Clin. Cancer Res. 2014, 20 (23): 5882–7. PMID 25451105. doi:10.1158/1078-0432.CCR-14-1165 .
^ O'Hagan HM, Mohammad HP, Baylin SB. Double strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island. PLOS Genetics. 2008, 4 (8): e1000155. PMC 2491723 . PMID 18704159. doi:10.1371/journal.pgen.1000155.
^ Cuozzo C, Porcellini A, Angrisano T, Morano A, Lee B, Di Pardo A, Messina S, Iuliano R, Fusco A, Santillo MR, Muller MT, Chiariotti L, Gottesman ME, Avvedimento EV. DNA damage, homology-directed repair, and DNA methylation. PLOS Genetics. Jul 2007, 3 (7): e110. PMC 1913100 . PMID 17616978. doi:10.1371/journal.pgen.0030110.
^ ^14.0 ^14.1 ^14.2 ^14.3 ^14.4 Yang J, Xu Z, Li J, Zhang R, Zhang G, Ji H, Song B, Chen Z. XPC epigenetic silence coupled with p53 alteration has a significant impact on bladder cancer outcome. J. Urol. 2010, 184 (1): 336–43. PMID 20488473. doi:10.1016/j.juro.2010.03.044.
^ ^15.0 ^15.1 ^15.2 Yeh KT, Wu YH, Lee MC, Wang L, Li CT, Chen CY, Lee H. XPC mRNA level may predict relapse in never-smokers with non-small cell lung cancers. Ann. Surg. Oncol. 2012, 19 (3): 734–42. PMID 21861227. S2CID 19154489. doi:10.1245/s10434-011-1992-9.
^ Hatano K, Kumar B, Zhang Y, Coulter JB, Hedayati M, Mears B, Ni X, Kudrolli TA, Chowdhury WH, Rodriguez R, DeWeese TL, Lupold SE. A functional screen identifies miRNAs that inhibit DNA repair and sensitize prostate cancer cells to ionizing radiation. Nucleic Acids Res. 2015, 43 (8): 4075–86. PMC 4417178 . PMID 25845598. doi:10.1093/nar/gkv273.
^ Shimizu Y, Iwai S, Hanaoka F, Sugasawa K. Xeroderma pigmentosum group C protein interacts physically and functionally with thymine DNA glycosylase. EMBO J. January 2003, 22 (1): 164–73. PMC 140069 . PMID 12505994. doi:10.1093/emboj/cdg016.
^ Araki M, Masutani C, Takemura M, Uchida A, Sugasawa K, Kondoh J, Ohkuma Y, Hanaoka F. Centrosome protein centrin 2/caltractin 1 is part of the xeroderma pigmentosum group C complex that initiates global genome nucleotide excision repair. J. Biol. Chem. June 2001, 276 (22): 18665–72. PMID 11279143. doi:10.1074/jbc.M100855200 .
^ Yokoi M, Masutani C, Maekawa T, Sugasawa K, Ohkuma Y, Hanaoka F. The xeroderma pigmentosum group C protein complex XPC-HR23B plays an important role in the recruitment of transcription factor IIH to damaged DNA. J. Biol. Chem. March 2000, 275 (13): 9870–5. PMID 10734143. doi:10.1074/jbc.275.13.9870 .

進一步閱讀

外部連結

GeneReviews/NIH/NCBI/UW 關於色素性干皮病的條目（頁面存檔備份，存於網際網路檔案館）

[1] 與XPC (基因)相關的疾病；在維基數據上查看/編輯參考.

[refGRCm38Ensembl-2] 2.0 ^2.1 ^2.2 GRCm38: Ensembl release 89: ENSMUSG00000030094 - Ensembl, May 2017

[3] Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] 5.0 ^5.1 ^5.2 Entrez Gene: XPC xeroderma pigmentosum, complementation group C.

[6] OMIM Entry - # 278720 - XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP C; XPC. [12 December 2014]. （原始內容存檔於2023-03-07）.

[pmid9734359-7] Sugasawa K, Ng JM, Masutani C, Iwai S, van der Spek PJ, Eker AP, Hanaoka F, Bootsma D, Hoeijmakers JH. Xeroderma pigmentosum group C protein complex is the initiator of global genome nucleotide excision repair. Mol. Cell. 1998, 2 (2): 223–32. PMID 9734359. doi:10.1016/s1097-2765(00)80132-x .

[Scharer-8] 8.0 ^8.1 Schärer OD. Nucleotide excision repair in eukaryotes. Cold Spring Harbor Perspectives in Biology. Oct 2013, 5 (10): a012609. PMC 3783044 . PMID 24086042. doi:10.1101/cshperspect.a012609.

[pmid18403632-9] Kastan MB. DNA damage responses: mechanisms and roles in human disease: 2007 G.H.A. Clowes Memorial Award Lecture. Mol. Cancer Res. 2008, 6 (4): 517–24. PMID 18403632. doi:10.1158/1541-7786.MCR-08-0020 .

[pmid18082599-10] Harper JW, Elledge SJ. The DNA damage response: ten years after. Mol. Cell. 2007, 28 (5): 739–45. PMID 18082599. doi:10.1016/j.molcel.2007.11.015 .

[pmid25451105-11] Dietlein F, Reinhardt HC. Molecular pathways: exploiting tumor-specific molecular defects in DNA repair pathways for precision cancer therapy. Clin. Cancer Res. 2014, 20 (23): 5882–7. PMID 25451105. doi:10.1158/1078-0432.CCR-14-1165 .

[Hagan-12] O'Hagan HM, Mohammad HP, Baylin SB. Double strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island. PLOS Genetics. 2008, 4 (8): e1000155. PMC 2491723 . PMID 18704159. doi:10.1371/journal.pgen.1000155.

[Cuozzo-13] Cuozzo C, Porcellini A, Angrisano T, Morano A, Lee B, Di Pardo A, Messina S, Iuliano R, Fusco A, Santillo MR, Muller MT, Chiariotti L, Gottesman ME, Avvedimento EV. DNA damage, homology-directed repair, and DNA methylation. PLOS Genetics. Jul 2007, 3 (7): e110. PMC 1913100 . PMID 17616978. doi:10.1371/journal.pgen.0030110.

[Yang-14] 14.0 ^14.1 ^14.2 ^14.3 ^14.4 Yang J, Xu Z, Li J, Zhang R, Zhang G, Ji H, Song B, Chen Z. XPC epigenetic silence coupled with p53 alteration has a significant impact on bladder cancer outcome. J. Urol. 2010, 184 (1): 336–43. PMID 20488473. doi:10.1016/j.juro.2010.03.044.

[Yeh-15] 15.0 ^15.1 ^15.2 Yeh KT, Wu YH, Lee MC, Wang L, Li CT, Chen CY, Lee H. XPC mRNA level may predict relapse in never-smokers with non-small cell lung cancers. Ann. Surg. Oncol. 2012, 19 (3): 734–42. PMID 21861227. S2CID 19154489. doi:10.1245/s10434-011-1992-9.

[pmid25845598-16] Hatano K, Kumar B, Zhang Y, Coulter JB, Hedayati M, Mears B, Ni X, Kudrolli TA, Chowdhury WH, Rodriguez R, DeWeese TL, Lupold SE. A functional screen identifies miRNAs that inhibit DNA repair and sensitize prostate cancer cells to ionizing radiation. Nucleic Acids Res. 2015, 43 (8): 4075–86. PMC 4417178 . PMID 25845598. doi:10.1093/nar/gkv273.

[pmid12505994-17] Shimizu Y, Iwai S, Hanaoka F, Sugasawa K. Xeroderma pigmentosum group C protein interacts physically and functionally with thymine DNA glycosylase. EMBO J. January 2003, 22 (1): 164–73. PMC 140069 . PMID 12505994. doi:10.1093/emboj/cdg016.

[pmid11279143-18] Araki M, Masutani C, Takemura M, Uchida A, Sugasawa K, Kondoh J, Ohkuma Y, Hanaoka F. Centrosome protein centrin 2/caltractin 1 is part of the xeroderma pigmentosum group C complex that initiates global genome nucleotide excision repair. J. Biol. Chem. June 2001, 276 (22): 18665–72. PMID 11279143. doi:10.1074/jbc.M100855200 .

[pmid10734143-19] Yokoi M, Masutani C, Maekawa T, Sugasawa K, Ohkuma Y, Hanaoka F. The xeroderma pigmentosum group C protein complex XPC-HR23B plays an important role in the recruitment of transcription factor IIH to damaged DNA. J. Biol. Chem. March 2000, 275 (13): 9870–5. PMID 10734143. doi:10.1074/jbc.275.13.9870 .

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