8ya8

Structural highlights

Disease

RTEL1_HUMAN Dyskeratosis congenita;Idiopathic pulmonary fibrosis;Hoyeraal-Hreidarsson syndrome. The disease is caused by variants affecting the gene represented in this entry. RTEL1 mutations have also been found in patients with a dyskeratosis congenita-like phenotype consisting of one feature of dyskeratosis congenita and short telomeres, in the absence of the typical DKC diagnostic triad (PubMed:23329068).^[1] The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.

Function

RTEL1_HUMAN ATP-dependent DNA helicase implicated in telomere-length regulation, DNA repair and the maintenance of genomic stability. Acts as an anti-recombinase to counteract toxic recombination and limit crossover during meiosis. Regulates meiotic recombination and crossover homeostasis by physically dissociating strand invasion events and thereby promotes noncrossover repair by meiotic synthesis dependent strand annealing (SDSA) as well as disassembly of D loop recombination intermediates. Also disassembles T loops and prevents telomere fragility by counteracting telomeric G4-DNA structures, which together ensure the dynamics and stability of the telomere.[HAMAP-Rule:MF_03065]^{[2] [3] [4]}

References

1. ↑ Ballew BJ, Yeager M, Jacobs K, Giri N, Boland J, Burdett L, Alter BP, Savage SA. Germline mutations of regulator of telomere elongation helicase 1, RTEL1, in Dyskeratosis congenita. Hum Genet. 2013 Apr;132(4):473-80. PMID:23329068 doi:10.1007/s00439-013-1265-8
2. ↑ Barber LJ, Youds JL, Ward JD, McIlwraith MJ, O'Neil NJ, Petalcorin MI, Martin JS, Collis SJ, Cantor SB, Auclair M, Tissenbaum H, West SC, Rose AM, Boulton SJ. RTEL1 maintains genomic stability by suppressing homologous recombination. Cell. 2008 Oct 17;135(2):261-71. PMID:18957201 doi:10.1016/j.cell.2008.08.016
3. ↑ Walne AJ, Vulliamy T, Kirwan M, Plagnol V, Dokal I. Constitutional mutations in RTEL1 cause severe dyskeratosis congenita. Am J Hum Genet. 2013 Mar 7;92(3):448-53. PMID:23453664 doi:10.1016/j.ajhg.2013.02.001
4. ↑ Ballew BJ, Joseph V, De S, Sarek G, Vannier JB, Stracker T, Schrader KA, Small TN, O'Reilly R, Manschreck C, Harlan Fleischut MM, Zhang L, Sullivan J, Stratton K, Yeager M, Jacobs K, Giri N, Alter BP, Boland J, Burdett L, Offit K, Boulton SJ, Savage SA, Petrini JH. A recessive founder mutation in regulator of telomere elongation helicase 1, RTEL1, underlies severe immunodeficiency and features of Hoyeraal Hreidarsson syndrome. PLoS Genet. 2013 Aug;9(8):e1003695. PMID:24009516 doi:10.1371/journal.pgen.1003695