XPC (基因)

XPC (基因)
已知的结构
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	2A4J、2GGM、2OBH、2RVB
识别号
别名	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
相关疾病
	xeroderma pigmentosum group C
基因位置（小鼠）
染色体	小鼠6号染色体
终止	91,492,870 bp
RNA表达模式
	查阅更多表达数据
基因本体
分子功能	• DNA结合; • heteroduplex DNA loop binding; • bubble DNA binding; • single-stranded DNA binding; • damaged DNA binding; • 血浆蛋白结合; • 大分子复合物结合;
细胞组分	• 细胞质; • 细胞膜; • 核质; • XPC complex; • 核仁; • nucleotide-excision repair factor 2 complex; • 细胞核; • 线粒体; • 细胞内膜结合细胞器; • nucleotide-excision repair complex;
生物学过程	• 核苷酸切除修复; • 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错配修复; • response to UV-B; • UV-damage excision repair; • DNA修复; • 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
	维基数据
查看/编辑人类	查看/编辑小鼠

互补组 C 型色素性皮肤病又称 XPC，是一种人体中由XPC基因编码的蛋白质。 XPC 参与核苷酸切除修复过程中对大块 DNA 加合物的识别。 ^[5]它位于3号染色体上^[6]。

功能

该基因编码核苷酸切除修复（NER）途径的一个组成部分。 NER通路涉及多种成分，包括着色性干皮病（XP）AG和V、科凯恩综合症（CS）A和B、毛发硫营养不良（TTD）A组等。该成分XPC在全球基因组 NER 的早期步骤，特别是损伤识别、开放复合物形成和修复蛋白复合物形成。 ^[5]

XPC-RAD23B 复合物是全局基因组核苷酸切除修复(GG-NER) 中的初始损伤识别因子。 ^[7] XPC-RAD23B 可识别多种热力学破坏 DNA 双链体稳定性的损伤，包括 UV 诱导的光产物（环嘧啶二聚体和 6-4 光产物）、环境诱变剂（如苯并[a]芘或各种芳香胺）形成的加合物、某些氧化内源性病变，例如环嘌呤和癌症化疗药物（例如顺铂）形成的加合物。 XPC-RAD23B 的存在是其他核心NER因子的组装以及体外和体内 NER 途径进展所必需的。 ^[8]尽管大多数研究都是使用 XPC-RAD23B 进行的，但它是与 centrin-2（钙调蛋白家族的钙结合蛋白）三聚体复合物的一部分。 ^[8]

临床意义

该基因或其他一些 NER 成分的突变会导致色素性干皮病，这是一种罕见的常染色体隐性遗传疾病，其特征是对阳光的敏感性增加，并在早期发展为癌症。 ^[5]

癌症

DNA 损伤似乎是癌症的主要原因^[9] ，而 DNA 修复基因的缺陷可能是多种癌症的根源。 ^[10] ^[11]如果DNA修复有缺陷，DNA损伤就会累积。这种过度的 DNA 损伤可能会由于易出错的跨损伤合成而增加突变。过度的 DNA 损伤还可能增加由于 DNA 修复过程中的错误而导致的表观遗传改变。 ^[12] ^[13]这种突变和表观遗传改变可能会导致癌症。

DNA 修复基因表达的减少（通常由启动子高甲基化等表观遗传改变引起）在癌症中非常常见，并且通常比癌症中 DNA 修复基因的突变缺陷更常见。^{[来源请求]}</link>^{[需要引用]}下表显示 XPC 表达在膀胱癌和非小细胞肺癌中经常发生表观遗传性降低，并且还显示 XPC 在这些癌症的晚期阶段更频繁地降低。

癌症中 XPC 表达降低的频率，并分别标明癌症的分期
癌症	频率	参考号
膀胱癌	50%	^[14]
低度恶性潜能乳头状尿路上皮肿瘤	35%	^[14]
低度恶性乳头状膀胱癌	42%	^[14]
高级别乳头状膀胱癌	65%	^[14]
非小细胞肺癌（NSCLC）	70%	^[15]
非小细胞肺癌 I 期	62%	^[15]
非小细胞肺癌 II-III 期	77%	^[15]

虽然XPC基因启动子区域的表观遗传高甲基化与 XPC 的低表达相关， ^[14] XPC的另一种表观遗传抑制模式也可能通过microRNA miR-890 的过度表达而发生。 ^[16]

互动

XPC（基因）已被证明与ABCA1 、 ^[17] CETN2 ^[18]和XPB相互作用。 ^[19]

参考

^ 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]. （原始内容存档于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 .

进一步阅读

外部链接

GeneReviews/NIH/NCBI/UW 关于色素性干皮病的条目（页面存档备份，存于互联网档案馆）

[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]. （原始内容存档于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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