BRCA1: Perbedaan antara revisi

BRCA1 adalah bagian dari kompleks protein yang berfungsi memperbaiki [[Perbaikan DNA|kerusakan untai ganda]] pada DNA. Ketika DNA mengalami kerusakan, untaian pada DNA tersebut akan terputus. Terkadang hanya satu untai yang putus, terkadang kedua untai putus secara bersamaan. Agen pengikat silang DNA (''DNA'' ''cross-linking agent'') adalah salah satu penyebab utama dari kerusakan kromosom dan DNA. Pemutusan untai ganda (''double strand breaks'') terjadi sebagai intermediet setelah ikatan silang ini dihilangkan. Mutasi bialelik pada ''BRCA1'' telah diidentifikasi bertanggung jawab atas [[Anemia Fanconi]], Complementation Group S (FA-S), penyakit genetik yang terkait dengan hipersensitivitas terhadap agen pengikat silang DNA.<ref>{{Cite journal|last=Sawyer|first=Sarah L.|last2=Tian|first2=Lei|last3=Kähkönen|first3=Marketta|last4=Schwartzentruber|first4=Jeremy|last5=Kircher|first5=Martin|last6=University of Washington Centre for Mendelian Genomics|last7=FORGE Canada Consortium|last8=Majewski|first8=Jacek|last9=Dyment|first9=David A.|date=2015-02-01|title=Biallelic Mutations in BRCA1 Cause a New Fanconi Anemia Subtype|url=https://aacrjournals.org/cancerdiscovery/article/5/2/135/4638/Biallelic-Mutations-in-BRCA1-Cause-a-New-Fanconi|journal=Cancer Discovery|language=en|volume=5|issue=2|pages=135–142|doi=10.1158/2159-8290.CD-14-1156|issn=2159-8274|pmc=PMC4320660|pmid=25472942}}</ref>

== Ekspresi ''BRCA1'' yang rendah pada kanker payudara dan ovarium ==

Ekspresi ''BRCA1'' berkurang atau tidak terdeteksi pada sebagian besar kanker payudara duktal tingkat tinggi (''high grade ductal breast cancers'').<ref>{{Cite journal|last=Wilson|first=Cindy A.|last2=Ramos|first2=Lillian|last3=Villaseñor|first3=Maria R.|last4=Anders|first4=Karl H.|last5=Press|first5=Michael F.|last6=Clarke|first6=Kathy|last7=Karlan|first7=Beth|last8=Chen|first8=Jun-Jie|last9=Scully|first9=Ralph|date=1999-02|title=Localization of human BRCA1 and its loss in high-grade, non-inherited breast carcinomas|url=https://www.nature.com/articles/ng0299_236|journal=Nature Genetics|language=en|volume=21|issue=2|pages=236–240|doi=10.1038/6029|issn=1061-4036}}</ref> Telah lama diketahui bahwa hilangnya aktivitas BRCA1, baik karena mutasi ''germ-line'' maupun karena penurunan regulasi ekspresi gen, menyebabkan pembentukan tumor pada jaringan-jaringan tertentu. Secara khusus, penurunan ekspresi ''BRCA1'' berkontribusi pada perkembangan tumor payudara sporadis (tidak diwariskan, terjadi secara spontan) dan yang diwariskan.<ref>{{Cite journal|last=Mueller|first=Christopher R|last2=Roskelley|first2=Calvin D|date=2002-02|title=Regulation of BRCA1 expression and its relationship to sporadic breast cancer|url=http://breast-cancer-research.biomedcentral.com/articles/10.1186/bcr557|journal=Breast Cancer Research|language=en|volume=5|issue=1|doi=10.1186/bcr557|issn=1465-542X|pmc=PMC154136|pmid=12559046}}</ref> Ekspresi ''BRCA1'' yang menurun bersifat tumorigenik, karena penurunan ekspresi ini memaikan peran penting dalam perbaikan kerusakan DNA, terutama pemutusan untai ganda, melalui jalur rekombinasi homolog yang berpotensi bebas dari kesalahan.<ref name=":4">{{Cite journal|last=Jacinto|first=F. V.|last2=Esteller|first2=M.|date=2007-07-01|title=Mutator pathways unleashed by epigenetic silencing in human cancer|url=https://academic.oup.com/mutage/article-lookup/doi/10.1093/mutage/gem009|journal=Mutagenesis|language=en|volume=22|issue=4|pages=247–253|doi=10.1093/mutage/gem009|issn=0267-8357}}</ref> Karena sel yang kekurangan protein BRCA1 cenderung memperbaiki kerusakan DNA dengan mekanisme alternatif yang lebih rentan terhadap kesalahan, penurunan atau penonaktifan protein ini menghasilkan mutasi dan penataan ulang kromosom (''chromosomal rearrangemen)'' yang dapat menyebabkan progresi kanker payudara.<ref name=":4" />

* [[H2AFX]]<ref name=pmid12485996/><ref name=pmid11927591/><ref name="pmid10959836">{{cite journal | vauthors = Paull TT, Rogakou EP, Yamazaki V, Kirchgessner CU, Gellert M, Bonner WM | title = A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage | journal = Curr. Biol. | volume = 10 | issue = 15 | pages = 886–95 | year = 2000 | pmid = 10959836 | doi = 10.1016/S0960-9822(00)00610-2 | doi-access = free }}</ref>

* [[MSH2]]<ref name="pmid10783165">{{cite journal | vauthors = Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J | title = BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures | journal = Genes Dev. | volume = 14 | issue = 8 | pages = 927–39 | date = April 2000 | pmid = 10783165 | pmc = 316544 | doi = 10.1101/gad.14.8.927}}</ref><ref name="pmid11498787"/>

* [[MSH3]]<ref name="pmid11498787" /><ref name="pmid14578343">{{cite journal | vauthors = Rodriguez M, Yu X, Chen J, Songyang Z | title = Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains | journal = J. Biol. Chem. | volume = 278 | issue = 52 | pages = 52914–8 | date = December 2003 | pmid = 14578343 | doi = 10.1074/jbc.C300407200 | doi-access = free }}</ref>

* [[MSH6]]<ref name=pmid10783165/><ref name="pmid11498787"/>

* [[Myc]]<ref name="pmid9788437"/><ref name=pmid11916966/><ref name="pmid14612409">{{cite journal | vauthors = Xiong J, Fan S, Meng Q, Schramm L, Wang C, Bouzahza B, Zhou J, Zafonte B, Goldberg ID, Haddad BR, Pestell RG, Rosen EM | title = BRCA1 inhibition of telomerase activity in cultured cells | journal = Mol. Cell. Biol. | volume = 23 | issue = 23 | pages = 8668–90 | date = December 2003 | pmid = 14612409 | pmc = 262673 | doi = 10.1128/MCB.23.23.8668-8690.2003 }}</ref><ref name="pmid12646176">{{cite journal | vauthors = Zhou C, Liu J | title = Inhibition of human telomerase reverse transcriptase gene expression by BRCA1 in human ovarian cancer cells | journal = Biochem. Biophys. Res. Commun. | volume = 303 | issue = 1 | pages = 130–6 | date = March 2003 | pmid = 12646176 | doi = 10.1016/S0006-291X(03)00318-8 }}</ref>

* [[NPM1]]<ref name=pmid15184379/>