Baeloji ea Limolek'hule ea Livaerase tsa DNA
Livaerase tsa DNA ke sehlopha sa livaerase tseo lintho tsa tsona tsa lefutso li entsoeng ka deoxyribonucleic acid (DNA). Ho fapana le livaerase tsa RNA, tseo ka kakaretso li ikatisang ka potlako 'me li na le sekhahla se phahameng sa liphetoho, livaerase tsa DNA li atisa ho ba le botsitso bo eketsehileng ba liphatsa tsa lefutso hobane DNA e hanela liphoso tsa ho ikatisa. Leha ho le joalo, botsitso ha bo bolele hore ha bo na kotsi: livaerase tse fapaneng tsa DNA li ka baka mafu a tebileng ho batho, liphoofolong le limela, ho tloha ho tšoaetso e matla ho isa ho tšoaetso e patiloeng le kankere. Sengoloa sena se tšohla likhopolo tsa bohlokoa baelojing ea limolek'hule tsa livaerase tsa DNA, ho kenyeletsoa sebopeho sa genome, maano a ho ikatisa, tlhahiso ea liphatsa tsa lefutso, likamano le lisele tse amohelang, le litlamorao tsa tsona bophelong bo botle le theknoloji ea baeloji.
Litšobotsi tse akaretsang le ho hlophisoa ha li-genome
Li-genome tsa vaerase ea DNA e ka ba DNA e nang le mela e 'meli (dsDNA) kapa DNA e nang le mela e le 'ngoe (ssDNA). Ho batho, livaerase tse ngata tsa bohlokoa tsa DNA li nkiloe ho dsDNA, mohlala, Herpesviridae (HSV, VZV, CMV, EBV), Adenoviridae, Poxviridae, le Papillomaviridae (HPV). Mohlala o tsebahalang oa ssDNA ke Parvoviridae. Libopeho tsa liphatsa tsa lefutso le tsona lia fapana: tse ling li na le mela e otlolohileng (mohlala, adenoviruses, herpesviruses), tse ling li chitja (mohlala, papillomaviruses, polyomaviruses), 'me tse ling li na le mehatla e khethehileng ea ho qetela e thusang ho ikatisa kapa ho paka.
Boholo ba genome ea livaerase tsa DNA le bona boa fapana. Li-Parvovirus li na le li-genome tse nyane, tse ka bang 5 kb, ha li-poxvirus li ka fihla ho feta 150–300 kb. Boholo ba genome bo amana le tekanyo ea "boikemelo" ba vaerase: livaerase tse kholo tsa DNA hangata li na le li-enzyme tsa tsona tsa ho ikatisa le ho ngola, ha li-genome tse nyane li itšetlehile haholo ka mechini ea sele e moamoheli.
Sebopeho sa dikarolwana le ho kena ha tsona ka hara disele
Livaerase tsa DNA ka kakaretso li na le protheine ea capsid e sireletsang genome. Tse ngata ke icosahedral (livaerase tsa adeno, HPV), ha livaerase tsa pox li na le sebopeho se rarahaneng. Livaerase tse ling tsa DNA tse koahetsoeng, tse kang livaerase tsa herpes, li fumana lera ho tsoa sele e amohelang 'me li jara li-glycoprotein bakeng sa ho tlama ho li-receptor tsa bokaholimo ba sele.
Mokhahlelo oa pele oa tšoaetso o kenyelletsa ho lemoha li-receptor le ho kena ha vaerase ka endocytosis, membrane fusion, kapa mekhoa e meng. Kamora ho kena, vaerase e tlameha ho isa DNA ea eona sebakeng sa ho ikatisa. Livaerase tse ngata tsa DNA li ikatisa ka har'a nucleus, li hloka hore genome ea tsona e fete ka har'a masoba a nyutlelie. Mokhelo o moholo ke livaerase tsa pox, tse tlatsang ho ikatisa le ho ngola ka har'a cytoplasm hobane li na le li-enzyme tse ngata tsa tsona.
Maano a ho ikatisa ha liphatsa tsa lefutso tsa kokoana-hloko ea DNA
Ho pheta-pheta ha DNA ea vaerase ke karolo ea bohlokoa ea baeloji ea limolek'hule tsa vaerase: kamoo DNA ea vaerase e hlahisoang kateng ka ho sebelisa kapa ho nkela mechini ea sele sebaka.
1. Livaerase tse nyane tsa DNA le ho itšetleha ka moamoheli
Livaerase tsa Papilloma le livaerase tsa polyoma li itšetlehile haholo ka enzyme ea DNA polymerase ea sele. Hobane DNA polymerase ea sele e sebetsa haholo nakong ea mohato oa S oa potoloho ea sele, livaerase tsena li thehile maano a ho "sutumelletsa" sele mohatong oa ho ikatisa. Liprotheine tsa pele tse kang E6 le E7 ho HPV li sitisa balaoli ba potoloho ea sele (mohlala, p53 le Rb), li lumella sele ho tsoela pele ho arohana le ho fana ka tikoloho e ntle bakeng sa ho ikatisa ha DNA ea vaerase.
2. Livaerase tse kholo tsa DNA le lienzyme tsa tsona
Li-poxvirus li na le DNA polymerase, li-enzyme tse sebetsanang le mRNA, le lintlha tsa transcription, tse li nolofalletsang ho ikatisa ka har'a cytoplasm. Li-herpesvirus li oela pakeng tsa tsona: li-herpesvirus tse ngata li sebelisa polymerase ea tsona ea DNA ea vaerase empa li ntse li itšetlehile ka lintlha tse ling tsa nyutlelie tse amohelang. Ho ikatisa ha Herpesvirus hangata ho kenyelletsa ho thehoa ha "likarolo tsa ho ikatisa" ka har'a nucleus, moo liprotheine tsa ho ikatisa li kopanang 'me DNA ea vaerase e hlahisoa ka matla.
3. Mekhoa e fapaneng ea ho ikatisa
– Ho pheta-pheta ha Theta hangata ho etsahala ka har'a li-genome tse chitja, tse tšoanang le ho pheta-pheta ha plasmid.
– Ho ikatisa ha circle e rotang ho atile haholo ho di-herpesvirus, ho hlahisa di-concatemers tse telele tsa DNA tse kgaolwang nakong ya ho paka.
– Ho falla ha Strand ho sebediswa ke adenovirus, e thuswang ke diprotheine tse qetellang tse kgomarelang dipheletsong tsa DNA e le di-primer.
– ssDNA → dsDNA e mahareng ho parvovirus: DNA e nang le stranded e le 'ngoe e fetoloa pele ho ba foromo ea dsDNA ke li-enzyme tsa sele pele ho phetolelo le ho ikatisa ho eketsehileng.
Polelo ea liphatsa tsa lefutso: mekhahlelo ea "pele" le "ea morao"
Ponahalo ea liphatsa tsa lefutso tsa kokoana-hloko ea DNA hangata e laoloa ka nakoana. Ka khopolo-taba, liphatsa tsa lefutso tsa "pele" li hlahisoa pele ho lokisa tikoloho ea sele bakeng sa ho ikatisa (mohlala, liprotheine tse laolang ho ngoloa ha mongolo, liprotheine tse laolang potoloho ea sele, polymerase ea DNA ea kokoana-hloko). Hang ha DNA ea kokoana-hloko e qala ho ikatisa, liphatsa tsa lefutso tsa "morao" li hlahisoa ho theha likarolo tsa sebopeho tse kang liprotheine tsa capsid le enfelopo, hammoho le lintlha tsa ho paka tsa genome.
Taolo ena e itshetlehile haholo hodima dipromothara, di-enhancer, le dintlha tsa ho ngolwa ha dikokwana-hloko/moamoheli. Dikokwana-hloko tsa DNA di boetse di laola tshebetso ya RNA: ho kopanya disele tse ding, polyadenylation, le botsitso ba mRNA. Dikokwana-hloko tsa Adeno, mohlala, di sebetsa e le mehlala ya bohlokwa baelojing ya dimolek'hule hobane dipatlisiso tsa adenovirus di lebisitse ho sibollweng ha ho kopanya disele tsa eukaryotic.
Tšebelisano le sesole sa 'mele le mekhoa ea ho qoba tšoaetso
Livaerase tsa DNA li tlameha ho hlola litšireletso tsa moamoheli tse kang li-interferons, litsela tsa ho lemoha DNA ka cytosolic (mohlala, cGAS–STING), le likarabelo tsa lisele tsa T le li-antibody. Livaerase tse ngata tsa DNA li hlahisitse liprotheine tse khethehileng ho thibela litsela tsena. Livaerase tse ling tsa herpes li hlahisa liprotheine tse fokotsang tlhahiso ea antigen ea MHC, e leng se etsang hore lisele tse tšoaelitsoeng li se ke tsa bonahala ho li-lymphocyte tsa T tse nang le chefo. Livaerase tsa pox li bile li na le liprotheine tse kang cytokine receptor tse monyang matšoao a 'mele a ho itšireletsa mafung ho fokotsa karabelo ea ho ruruha.
Ho phaella moo, divaerase tsa DNA di ka dula di ipatile. Divaerase tsa Herpes di tsebahala ka ho hlahisa ditshwaetso tse ipatileng di-neuron (HSV) kapa diseleng tsa B (EBV). Nakong ya mohato o ipatileng, tlhahiso ya dijini tsa vaerase e nyane haholo, e leng se etsang hore ho be thata hore sesole sa mmele se di lemohe, empa vaerase e boloka genome ya yona mme e ka boela ya sebetsa ha boemo ba moamoheli bo fokola.
Ho kopanngoa ha liphatsa tsa lefutso le kamano ea tsona le kankere
Livaerase tse ling tsa DNA li ka kopana le genome ea moamoheli kapa tsa boloka li-episome tse tsitsitseng. Ho kopana ha se kamehla ho tlamang bakeng sa ho ikatisa, empa ha ho etsahala, ho ka ba le litlamorao tse kholo tsa baeloji. Li-HPV tse kotsi haholo (mohlala, mefuta ea 16 le 18) li fumanoa li kopantsoe khafetsa mofetšeng oa molomo oa popelo, li eketsa tlhahiso ea E6/E7, e sitisang p53/Rb le ho khothalletsa phetoho ea sele. EBV le herpesvirus e amanang le Kaposi's sarcoma (KSHV) le tsona li hokahantsoe le mefuta e fapaneng ea mofetše ka motsoako oa latency, modulation ea sele le ho ruruha ho sa foleng.
Lithuto tsa baeloji ea limolek'hule tsa likokoana-hloko tsa DNA li bontša hore mofetše o amanang le kokoana-hloko ha se feela phello ea "boteng ba kokoana-hloko," empa ho e-na le hoo ke tšebelisano e rarahaneng pakeng tsa liphatsa tsa lefutso tsa kokoana-hloko, taolo ea potoloho ea sele, tokiso ea DNA, le likhatello tsa khetho liseleng tse tšoaelitsoeng.
Ho bokella le ho lokolla li-virion
Ka mora hore genome e hlahisoe mme diprotheine tsa sebopeho di hlahiswe, virion e a kopanngwa. Divaerase tse ngata tsa DNA di bokella capsid ka hara nucleus, ebe di kenya DNA ka hara mechini ya ho paka. Divaerase tsa Herpes, mohlala, di haha di-capsid tsa tsona ka hara nucleus, ebe di fumana enfelopo ka tshebetso ya mehato e mengata e kenyeletsang lera la nyutlelie le di-organelle tse ntshang secretory. Ka lehlakoreng le leng, divaerase tse sa kwahelwang tse kang di-adenovirus hangata di lokollwa ha sele e qhibidihile.
Mokhahlelo oa kopano hangata o reretsoe kalafo hobane o kenyelletsa likamano tse itseng tsa protheine le protheine. Leha e le phephetso ho feta ho shebana le li-enzyme, mokhoa ona o qala ho hlahlojoa ntlafatsong ea meriana ea kokoana-hloko ea moloko o latelang.
Litlamorao tsa bongaka le tsa theknoloji ea baeloji
Ho utloisisa baeloji ea limolek'hule tsa likokoana-hloko tsa DNA ho lebisitse nts'etsopele ea mahlale le mekhoa e fapaneng ea phekolo. Mohlala, liente tsa HPV tse thehiloeng likarolong tse kang tsa kokoana-hloko li fokolitse sekhahla sa mefuta e kotsi ea tšoaetso. Bakeng sa li-herpesvirus, meriana e kang acyclovir e shebane ka ho khetheha le polymerase ea DNA ea kokoana-hloko. Ka lehlakoreng le leng, li-adenovirus li sebelisoa e le li-vector tsa liente le phekolo ea liphatsa tsa lefutso hobane li fana ka DNA ka katleho liseleng 'me li ka etsoa hore li se ke tsa baka mafu.
Laboratoring, divaerase tsa DNA di boetse di sebetsa e le "disebediswa" tsa ho utlwisisa mekgwa ya motheo ya disele tsa eukaryotic, ho tloha taolong ya mongolo, ho kopanya, le ho ikatisa ha DNA ho isa tshenyong le ditseleng tsa tokiso ya DNA. Ka mantswe a mang, divaerase ha di bonwe e le disosa tsa mafu feela empa hape e le mehlala ya baeloji e thusang ho sibolla melao ya motheo ya bophelo ba sele.
Ho koala
Baeloji ea limolek'hule ea livaerase tsa DNA ke lefapha la thuto ea hore na livaerase tse thehiloeng ho DNA li kena joang liseleng, li hlahisa liphatsa tsa lefutso, li ikatisa liphatsa tsa tsona tsa lefutso, li qoba sesole sa 'mele,' me li namela liseleng tse ling. Mefuta e fapaneng ea maano a sebelisoang—ho tloha ho itšetleheng ka mechini ea sele ho isa ho ikemeleng ka lienzyme tsa tsona—e bontša ho ikamahanya ho ikhethang ha livaerase. Ho utloisisa mehato ena ea limolek'hule ha ho bohlokoa feela bakeng sa ho laola mafu empa hape ho bula menyetla e meholo bakeng sa nts'etsopele ea liente, meriana ea antiviral, le mahlale a bongaka a thehiloeng ho livaerase. Ka lipatlisiso tse ling, livaerase tsa DNA li tla tsoela pele ho fana ka fensetere ea hore na lisele li sebetsa joang, hammoho le phephetso e kholo bophelong ba sechaba ba sejoale-joale.
