DCLRE1B
Description
The DCLRE1B (DNA cross-link repair 1B) is a protein-coding gene located on chromosome 1.
DNA cross-link repair 1B protein is a protein that in humans is encoded by the DCLRE1B gene. DNA interstrand cross-links prevent strand separation, thereby physically blocking transcription, replication, and segregation of DNA. DCLRE1B is one of several evolutionarily conserved genes involved in repair of interstrand cross-links (Dronkert et al., 2000).[supplied by OMIM] The DCLRE1B/SNM1B/Apollo protein is a repair exonuclease that digests double-stranded and single-stranded DNA with a 5’ to 3’ directionality. Using an SNM1B/Apollo knockout mouse model, evidence was obtained that SNM1B/Apollo protein is required to protect telomeres against illegitimate non-homologous end joining that can result in genomic instability and consequently in multi-organ developmental failure. In a human patient with Hoyeraal-Hreidarsson syndrome, a dominant negative mutation in the SNM1B/Apollo gene was discovered. This mutation hampered the proper replication of telomeres, leading to major telomeric dysfunction and cellular senescence. SNM1B/Apollo protein appears to be a crucial factor in telomere maintenance, independent of its function in repairing DNA inter-strand crosslinks.
The DCLRE1B protein, also known as Apollo, is a 5'-3' exonuclease that plays a critical role in maintaining and protecting telomeres during DNA replication (S-phase). It prevents telomeres from fusing by protecting them from non-homologous end-joining (NHEJ) repair mechanisms. DCLRE1B is essential for the formation of telomeric loops (T loops), a structure that protects telomeres from degradation. This process is facilitated by the recruitment of DCLRE1B to the leading end of telomeres by the protein TERF2. DCLRE1B's exonuclease activity processes the leading-end telomeres after replication, generating a 3' single-stranded overhang that prevents blunt ends that are susceptible to end-joining reactions. This overhang also exposes the telomere end in a way that activates DNA repair pathways. DCLRE1B, along with TERF2, safeguards telomeres from replicative damage during replication by regulating the amount of DNA topoisomerase (TOP1, TOP2A, and TOP2B) required for telomere replication during fork passage, preventing aberrant telomere topology. DCLRE1B is also involved in the cellular response to DNA damage, specifically in the repair of DNA interstrand cross-links (ICLs) by promoting double-strand break formation. In the event of spindle stress, DCLRE1B participates in the prophase checkpoint. DCLRE1B possesses beta-lactamase activity, hydrolyzing penicillin G and nitrocefin but not other beta-lactam antibiotic classes like cephalosporins and carbapenems. DCLRE1B interacts directly with TERF2, as well as with MUS81, MRE11, FANCD2, HSPA2, HSPA8, HSPA14, and SPAG5.
DCLRE1B is also known as APOLLO, DKCB8, SNM1B, SNMIB.
