DCLRE1B

DCLRE1B
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	3BUA, 5AHO
Identifikatori
Aliasi	DCLRE1B
Vanjski ID-jevi	OMIM: 609683 MGI: 2156057 HomoloGene: 32553 GeneCards: DCLRE1B
Lokacija gena (čovjek)
Hrom.	Hromosom 1 (čovjek)
Kraj	113,914,086 bp
Lokacija gena (miš)
Hrom.	Hromosom 3 (miš)
Kraj	103,716,760 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• 5'-3' exonuclease activity; • 5'-3' exodeoxyribonuclease activity; • oštećeno vezivanje sa DNK; • GO:0001948, GO:0016582 vezivanje za proteine; • nuclease activity; • exonuclease activity; • hydrolase activity; • protein homodimerization activity; • GO:0032403 protein-containing complex binding;
Ćelijska komponenta	• citoplazma; • centrosom; • hromosom; • centar organizacije mikrotubula; • Telomera; • citoskelet; • jedro; • nukleoplazma; • nuclear body;
Biološki proces	• Kontrolna tačka ćelijskog ciklusa; • protection from non-homologous end joining at telomere; • telomeric 3' overhang formation; • cellular response to DNA damage stimulus; • double-strand break repair via nonhomologous end joining; • telomere maintenance; • telomeric loop formation; • GO:0100026 Popravka DNK; • nucleic acid phosphodiester bond hydrolysis; • telomere maintenance via telomere lengthening; • telomere capping; • interstrand cross-link repair; • mitotic cell cycle checkpoint signaling;
	Izvori:Amigo / QuickGO
Ortolozi
	64858
	140917
	ENSG00000118655
	ENSMUSG00000027845
	Q9H816
	Q8C7W7
	NM_022836; NM_001319946; NM_001319947; NM_001363690; NM_001363691
	NM_001025312; NM_133865
	NP_001306875; NP_001306876; NP_073747; NP_001350619; NP_001350620
	NP_001020483; NP_598626
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Protein 1B unakrsno-linkovanog popravka DNK jest protein koji je kod ljudi kodiran genom DCLRE1B sa hromosoma 1.^[5]

Amiokiselininska sekvenca

Dužina polipeptidnog lanca je 532 aminokiseline, a molekulska težina 60.002 Da.^[6]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MNGVLIPHTP	IAVDFWSLRR	AGTARLFFLS	HMHSDHTVGL	SSTWARPLYC
SPITAHLLHR	HLQVSKQWIQ	ALEVGESHVL	PLDEIGQETM	TVTLLDANHC
PGSVMFLFEG	YFGTILYTGD	FRYTPSMLKE	PALTLGKQIH	TLYLDNTNCN
PALVLPSRQE	AAHQIVQLIR	KHPQHNIKIG	LYSLGKESLL	EQLALEFQTW
VVLSPRRLEL	VQLLGLADVF	TVEEKAGRIH	AVDHMEICHS	NMLRWNQTHP
TIAILPTSRK	IHSSHPDIHV	IPYSDHSSYS	ELRAFVAALK	PCQVVPIVSR
RPCGGFQDSL	SPRISVPLIP	DSVQQYMSSS	SRKPSLLWLL	ERRLKRPRTQ
GVVFESPEES	ADQSQADRDS	KKAKKEKLSP	WPADLEKQPS	HHPLRIKKQL
FPDLYSKEWN	KAVPFCESQK	RVTMLTAPLG	FSVHLRSTDE	EFISQKTREE
IGLGSPLVPM	GDDDGGPEAT	GNQSAWMGHG	SPLSHSSKGT	PLLATEFRGL
ALKYLLTPVN	FFQAGYSSRR	FDQQVEKYHK	PC

Funkcija

Unakrsne veze DNK između lanaca sprečavaju njihovo razdvajanje, čime fizički blokiraju transkripciju, replikaciju i segregaciju DNK. DCLRE1B je jedan od nekoliko evolucijski konzerviranih gena koji su uključeni u popravku međulančanih unakrsnih veza (Dronkert et al., 2000), prema OMIM^[5]

DCLRE1B/SNM1B/Apolo protein je popravljačka egzonukleaza koja probavlja dvolančanu i jednolančanu DNK sa usmjerenošću od 5' do 3'.^[7]

Koristeći SNM1B/Apolo model nokaut-miša, dobijeni su dokazi da je protein SNM1B/Apolo potreban za zaštitu telomera od nelegitimnog nehomolognog spajanja krajeva koje može rezultirati genomskom nestabilnošću i posljedično u razvoju više organa.^[8]

Klinički značaj

Kod ljudskog pacijenta sa Hoyeraal-Hreidarssonovim sindromom, otkrivena je dominantna negativna mutacija u SNM1B/Apolo genu.^[9] Ova mutacija je ometala pravilnu replikaciju telomera, što je dovelo do velike telomerne disfunkcije i ćelijskog starenja. Čini se da je SNM1B/Apolo protein ključni faktor u održavanju telomera, neovisno o njegovoj funkciji u popravljanju međulančanih poprečnih veza DNK.^[9]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000118655 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000027845 - Ensembl, maj 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.
^ ^a ^b "Entrez Gene: DCLRE1B DNA cross-link repair 1B (PSO2 homolog, S. cerevisiae)".
^ "UniProt, Q9H816" (jezik: engleski). Pristupljeno 24. 11. 2021.
^ Sengerová B, Allerston CK, Abu M, Lee SY, Hartley J, Kiakos K, Schofield CJ, Hartley JA, Gileadi O, McHugh PJ (2012). "Characterization of the human SNM1A and SNM1B/Apollo DNA repair exonucleases". J. Biol. Chem. 287 (31): 26254–67. doi:10.1074/jbc.M112.367243. PMC 3406710. PMID 22692201.
^ Akhter S, Lam YC, Chang S, Legerski RJ (2010). "The telomeric protein SNM1B/Apollo is required for normal cell proliferation and embryonic development". Aging Cell. 9 (6): 1047–56. doi:10.1111/j.1474-9726.2010.00631.x. PMC 3719988. PMID 20854421.
^ ^a ^b Touzot F, Callebaut I, Soulier J, Gaillard L, Azerrad C, Durandy A, Fischer A, de Villartay JP, Revy P (2010). "Function of Apollo (SNM1B) at telomere highlighted by a splice variant identified in a patient with Hoyeraal-Hreidarsson syndrome". Proc. Natl. Acad. Sci. U.S.A. 107 (22): 10097–102. Bibcode:2010PNAS..10710097T. doi:10.1073/pnas.0914918107. PMC 2890423. PMID 20479256.

Dopunska literatura

Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
Demuth I, Digweed M, Concannon P (2004). "Human SNM1B is required for normal cellular response to both DNA interstrand crosslink-inducing agents and ionizing radiation". Oncogene. 23 (53): 8611–8. doi:10.1038/sj.onc.1207895. PMID 15467758.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Ishiai M, Kimura M, Namikoshi K, et al. (2004). "DNA cross-link repair protein SNM1A interacts with PIAS1 in nuclear focus formation". Mol. Cell. Biol. 24 (24): 10733–41. doi:10.1128/MCB.24.24.10733-10741.2004. PMC 533992. PMID 15572677.
Freibaum BD, Counter CM (2006). "hSnm1B is a novel telomere-associated protein". J. Biol. Chem. 281 (22): 15033–6. doi:10.1074/jbc.C600038200. PMID 16606622.
Gregory SG, Barlow KF, McLay KE, et al. (2006). "The DNA sequence and biological annotation of human chromosome 1". Nature. 441 (7091): 315–21. Bibcode:2006Natur.441..315G. doi:10.1038/nature04727. PMID 16710414.
Lenain C, Bauwens S, Amiard S, et al. (2006). "The Apollo 5' exonuclease functions together with TRF2 to protect telomeres from DNA repair". Curr. Biol. 16 (13): 1303–10. doi:10.1016/j.cub.2006.05.021. PMID 16730175.
van Overbeek M, de Lange T (2006). "Apollo, an Artemis-related nuclease, interacts with TRF2 and protects human telomeres in S phase". Curr. Biol. 16 (13): 1295–302. doi:10.1016/j.cub.2006.05.022. PMID 16730176. S2CID 121737.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000118655 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000027845 - Ensembl, maj 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] "Entrez Gene: DCLRE1B DNA cross-link repair 1B (PSO2 homolog, S. cerevisiae)".

[UniProt-6] "UniProt, Q9H816" (jezik: engleski). Pristupljeno 24. 11. 2021.

[pmid22692201-7] Sengerová B, Allerston CK, Abu M, Lee SY, Hartley J, Kiakos K, Schofield CJ, Hartley JA, Gileadi O, McHugh PJ (2012). "Characterization of the human SNM1A and SNM1B/Apollo DNA repair exonucleases". J. Biol. Chem. 287 (31): 26254–67. doi:10.1074/jbc.M112.367243. PMC 3406710. PMID 22692201.

[pmid20854421-8] Akhter S, Lam YC, Chang S, Legerski RJ (2010). "The telomeric protein SNM1B/Apollo is required for normal cell proliferation and embryonic development". Aging Cell. 9 (6): 1047–56. doi:10.1111/j.1474-9726.2010.00631.x. PMC 3719988. PMID 20854421.

[pmid20479256-9] Touzot F, Callebaut I, Soulier J, Gaillard L, Azerrad C, Durandy A, Fischer A, de Villartay JP, Revy P (2010). "Function of Apollo (SNM1B) at telomere highlighted by a splice variant identified in a patient with Hoyeraal-Hreidarsson syndrome". Proc. Natl. Acad. Sci. U.S.A. 107 (22): 10097–102. Bibcode:2010PNAS..10710097T. doi:10.1073/pnas.0914918107. PMC 2890423. PMID 20479256.

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