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DNA cross-link repair 1B protein (DCLRE1B)

Target: DCLRE1B
Molecular classification: Enzyme (5'-3' exonuclease), DNA repair protein, Member of the metallo-β-lactamase (MBL) superfamily, β-CASP nuclease subgroup

Overview

DNA cross-link repair 1B protein (DCLRE1B), also known as 5' exonuclease Apollo or SNM1B, is an evolutionarily conserved DNA repair enzyme in the metallo-β-lactamase (MBL) superfamily, functioning primarily as a 5'-3' exonuclease involved in the repair of DNA interstrand cross-links and the maintenance of telomere stability[1][2][4][5]. DCLRE1B digests damaged or cross-linked DNA, protecting telomeres from aberrant end-joining and supporting genomic stability, especially during replication[1][2][4][6]. It interacts with multiple DNA repair factors and the Fanconi anemia (FA) protein network, and its deficiency is associated with telomere dysfunction, genomic instability, and various human diseases including cancer and inherited telomeropathies[5][9]. Elevated DCLRE1B expression is associated with poor prognosis in several cancers, and it is being investigated as a prognostic biomarker, though no direct therapeutics currently target this enzyme[5][9].

Other names: 5' exonuclease ApolloSNM1BSNMIBhSNM1BFLJ12810FLJ13998APOLLOBeta-lactamase DCLRE1BDNA cross-link repair 1B proteinSNM1 homolog BPSO2 homolog (S. cerevisiae)DKCB8PSO2 homologbeta-lactamase DCLRE1B

Biological functions

DNA interstrand cross-link repairTelomere maintenance and protectionHomologous recombinationReplication fork maintenanceResponse to DNA damage (part of Fanconi anemia DNA repair pathway)Regulation of end-joining at telomeresControl of topological stress during telomere replication

Disease associations

Cancer (promotes tumor progression and predicts immunotherapy response, implicated in cancer stemness)Dyskeratosis congenita (including autosomal recessive type 8)Hoyeraal-Hreidarsson syndrome (telomere dysfunction)Spastic paraplegia 47 (autosomal recessive)Possibly other syndromes involving genome instability

Safety considerations

Potential for genomic instability if inhibited (risk of telomere dysfunction, chromosomal instability, and increased susceptibility to DNA damage)Possible impact on normal stem/progenitor cell function if targeted therapeutically

Biomarkers

DCLRE1B expression (prognostic biomarker for immune infiltration and clinical outcome in cancer, e.g., liver hepatocellular carcinoma and pancreatic cancer)

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