D
IPR049909

Regulator of telomere elongation helicase 1, harmonin homology domain

InterPro entry
Short nameHHD_RTEL1

Description

This entry represents a domain which appears to be similar to the N-terminal domain of the scaffolding protein harmonin, and therefore, it has been named as the harmonin homology domain (HHD), found C-terminal of these proteins. In human and some other mammals as well as in some fish species, this domain is found as two tandem ones, referred to as HHD1 and HHD2 (or HNL1/2)
[8, 7]
, while in plants and arthropods it is found as a single domain. HHD1/2 may mediate protein-protein interactions. It has been shown that the HHD1 domain from the human protein mediates interaction of RTEL1 with SLX4, which prevents replication-transcription collision through R-loop dissolution. Mutations in these domain are associateδ with Hoyeraal-Hreidarsson syndrome and pulmonary fibrosis
[8]
.

Regulator of telomere elongation helicase 1 (RTEL1) is the animal functional analogue of yeast Srs2, which is a DNA helicase and DNA-dependent ATPase involved in DNA repair and checkpoint recovery
[2]
. RTEL1 is an essential DNA helicase that disassembles a variety of DNA secondary structures to facilitate DNA replication, repair, and recombination processes, and to maintain both telomeric and genomic stability
[8, 4, 1, 6]
. It is recruited by Trf2 to telomeres in S phase to promote T-Loop unwinding
[5]
. It is also required for the export and the correct cytoplasmic trafficking of the small nuclear (sn) RNA pre-U2, a component of the major spliceosome complex
[3]
. Human RTEL1 is implicated in the etiology of Dyskeratosis congenital (DC, is an inherited bone marrow failure and cancer predisposition syndrome)
[11]
. Point mutations in its helicase domains, and truncations which result in loss of its C terminus have been discovered in DC families. RTEL1 is also a candidate gene influencing glioma susceptibility
[2, 10, 9]
.

References

1.A recessive founder mutation in regulator of telomere elongation helicase 1, RTEL1, underlies severe immunodeficiency and features of Hoyeraal Hreidarsson syndrome. 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. PLoS Genet. 9, e1003695, (2013). View articlePMID: 24009516

2.RTEL1 maintains genomic stability by suppressing homologous recombination. 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. Cell 135, 261-71, (2008). View articlePMID: 18957201

3.Human regulator of telomere elongation helicase 1 (RTEL1) is required for the nuclear and cytoplasmic trafficking of pre-U2 RNA. Schertzer M, Jouravleva K, Perderiset M, Dingli F, Loew D, Le Guen T, Bardoni B, de Villartay JP, Revy P, Londono-Vallejo A. Nucleic Acids Res. 43, 1834-47, (2015). View articlePMID: 25628358

4.RTEL1: functions of a disease-associated helicase. Vannier JB, Sarek G, Boulton SJ. Trends Cell Biol. 24, 416-25, (2014). View articlePMID: 24582487

5.TRF2 Recruits RTEL1 to Telomeres in S Phase to Promote T-Loop Unwinding. Sarek G, Vannier JB, Panier S, Petrini JH, Boulton SJ. Mol. Cell 57, 622-35, (2015). View articlePMID: 25620558

6.dRTEL1 is essential for the maintenance of Drosophila male germline stem cells. Yang Y, Kong R, Goh FG, Somers WG, Hime GR, Li Z, Cai Y. PLoS Genet 17, e1009834, (2021). PMID: 34644293

7.The many faces of the helicase RTEL1 at telomeres and beyond. Hourvitz N, Awad A, Tzfati Y. Trends Cell Biol S0962-8924(23)00135-6, (2023). View articlePMID: 37532653

8.Resonance assignment and secondary structure of the tandem harmonin homology domains of human RTEL1. Kumar N, Ghosh M, Manikandan P, Basak S, Deepa A, Singh M. Biomol NMR Assign 16, 159-164, (2022). View articlePMID: 35320499

9.Genome-wide association study of glioma and meta-analysis. Rajaraman P, Melin BS, Wang Z, McKean-Cowdin R, Michaud DS, Wang SS, Bondy M, Houlston R, Jenkins RB, Wrensch M, Yeager M, Ahlbom A, Albanes D, Andersson U, Freeman LE, Buring JE, Butler MA, Braganza M, Carreon T, Feychting M, Fleming SJ, Gapstur SM, Gaziano JM, Giles GG, Hallmans G, Henriksson R, Hoffman-Bolton J, Inskip PD, Johansen C, Kitahara CM, Lathrop M, Liu C, Le Marchand L, Linet MS, Lonn S, Peters U, Purdue MP, Rothman N, Ruder AM, Sanson M, Sesso HD, Severi G, Shu XO, Simon M, Stampfer M, Stevens VL, Visvanathan K, White E, Wolk A, Zeleniuch-Jacquotte A, Zheng W, Decker P, Enciso-Mora V, Fridley B, Gao YT, Kosel M, Lachance DH, Lau C, Rice T, Swerdlow A, Wiemels JL, Wiencke JK, Shete S, Xiang YB, Xiao Y, Hoover RN, Fraumeni JF Jr, Chatterjee N, Hartge P, Chanock SJ. Hum Genet 131, 1877-88, (2012). PMID: 22886559

10.Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility. Wrensch M, Jenkins RB, Chang JS, Yeh RF, Xiao Y, Decker PA, Ballman KV, Berger M, Buckner JC, Chang S, Giannini C, Halder C, Kollmeyer TM, Kosel ML, LaChance DH, McCoy L, O'Neill BP, Patoka J, Pico AR, Prados M, Quesenberry C, Rice T, Rynearson AL, Smirnov I, Tihan T, Wiemels J, Yang P, Wiencke JK. Nat Genet 41, 905-8, (2009). PMID: 19578366

11.Germline mutations of regulator of telomere elongation helicase 1, RTEL1, in Dyskeratosis congenita. Ballew BJ, Yeager M, Jacobs K, Giri N, Boland J, Burdett L, Alter BP, Savage SA. Hum Genet 132, 473-80, (2013). PMID: 23329068

Cross References

This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our Privacy Notice and Terms of Use.