RTEL1

This gene encodes a DNA helicase which functions in the stability, protection and elongation of telomeres and interacts with proteins in the shelterin complex known to protect telomeres during DNA replication. Mutations in this gene have been associated with dyskeratosis congenita and Hoyerall-Hreidarsson syndrome. Read-through transcription of this gene into the neighboring downstream gene, which encodes tumor necrosis factor receptor superfamily, member 6b, generates a non-coding transcript. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2013]

Full Name

Regulator Of Telomere Elongation Helicase 1

Function

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.

Biological Process

Biological Process DNA duplex unwindingBy SimilarityISS:BHF-UCL
Biological Process DNA repairIEA:UniProtKB-UniRule
Biological Process mitotic telomere maintenance via semi-conservative replicationBy SimilarityISS:BHF-UCL
Biological Process negative regulation of DNA recombinationISS:BHF-UCL
Biological Process negative regulation of t-circle formationManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process negative regulation of telomere maintenance in response to DNA damageISS:BHF-UCL
Biological Process positive regulation of telomere cappingManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process positive regulation of telomere maintenanceISS:BHF-UCL
Biological Process positive regulation of telomere maintenance via telomere lengtheningManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process positive regulation of telomeric loop disassemblyISS:BHF-UCL
Biological Process regulation of double-strand break repair via homologous recombinationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process replication fork processingBy SimilarityISS:BHF-UCL
Biological Process strand displacementISS:BHF-UCL
Biological Process telomere maintenanceManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process telomere maintenance in response to DNA damageISS:BHF-UCL
Biological Process telomeric loop disassemblyManual Assertion Based On ExperimentIMP:BHF-UCL

Cellular Location

Nucleus
Colocalizes with PCNA within the replication foci in S-phase cells.

Involvement in disease

Dyskeratosis congenita, autosomal recessive, 5 (DKCB5):
A form of dyskeratosis congenita, a rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. DKCB5 is characterized by onset of bone marrow failure and immunodeficiency in early childhood. Most patients also have growth and developmental delay and cerebellar hypoplasia, consistent with a clinical diagnosis of Hoyeraal-Hreidarsson syndrome.
Dyskeratosis congenita, autosomal dominant, 4 (DKCA4):
A rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy.
Pulmonary fibrosis, and/or bone marrow failure, telomere-related, 3 (PFBMFT3):
An autosomal dominant disease associated with shortened telomeres. Pulmonary fibrosis is the most common manifestation. Other manifestations include aplastic anemia due to bone marrow failure, hepatic fibrosis, and increased cancer risk, particularly myelodysplastic syndrome and acute myeloid leukemia. Phenotype, age at onset, and severity are determined by telomere length.