DCLRE1B explained

DNA cross-link repair 1B protein is a protein that in humans is encoded by the DCLRE1B gene.^[1]

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]

Function

The DCLRE1B/SNM1B/Apollo protein is a repair exonuclease that digests double-stranded and single-stranded DNA with a 5’ to 3’ directionality.^[2]

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.^[3]

In a human patient with Hoyeraal-Hreidarsson syndrome, a dominant negative mutation in the SNM1B/Apollo gene was discovered.^[4] 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.

Further reading

• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Ota T, Suzuki Y, Nishikawa T . Complete sequencing and characterization of 21,243 full-length human cDNAs. . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . etal. free .
• Demuth I, Digweed M, Concannon P . Human SNM1B is required for normal cellular response to both DNA interstrand crosslink-inducing agents and ionizing radiation. . Oncogene . 23 . 53 . 8611–8 . 2004 . 15467758 . 10.1038/sj.onc.1207895 . 10082205 .
• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Ishiai M, Kimura M, Namikoshi K . DNA cross-link repair protein SNM1A interacts with PIAS1 in nuclear focus formation. . Mol. Cell. Biol. . 24 . 24 . 10733–41 . 2004 . 15572677 . 10.1128/MCB.24.24.10733-10741.2004 . 533992 . etal.
• Freibaum BD, Counter CM . hSnm1B is a novel telomere-associated protein. . J. Biol. Chem. . 281 . 22 . 15033–6 . 2006 . 16606622 . 10.1074/jbc.C600038200 . free .
• Gregory SG, Barlow KF, McLay KE . The DNA sequence and biological annotation of human chromosome 1. . Nature . 441 . 7091 . 315–21 . 2006 . 16710414 . 10.1038/nature04727 . 2006Natur.441..315G . etal. free .
• Lenain C, Bauwens S, Amiard S . The Apollo 5' exonuclease functions together with TRF2 to protect telomeres from DNA repair. . Curr. Biol. . 16 . 13 . 1303–10 . 2006 . 16730175 . 10.1016/j.cub.2006.05.021 . etal. free . 2006CBio...16.1303L .
• van Overbeek M, de Lange T . Apollo, an Artemis-related nuclease, interacts with TRF2 and protects human telomeres in S phase. . Curr. Biol. . 16 . 13 . 1295–302 . 2006 . 16730176 . 10.1016/j.cub.2006.05.022 . 121737 . free . 2006CBio...16.1295V .

Notes and References

1. Web site: Entrez Gene: DCLRE1B DNA cross-link repair 1B (PSO2 homolog, S. cerevisiae).
2. Sengerová B, Allerston CK, Abu M, Lee SY, Hartley J, Kiakos K, Schofield CJ, Hartley JA, Gileadi O, McHugh PJ . Characterization of the human SNM1A and SNM1B/Apollo DNA repair exonucleases . J. Biol. Chem. . 287 . 31 . 26254–67 . 2012 . 22692201 . 3406710 . 10.1074/jbc.M112.367243 . free .
3. Akhter S, Lam YC, Chang S, Legerski RJ . The telomeric protein SNM1B/Apollo is required for normal cell proliferation and embryonic development . Aging Cell . 9 . 6 . 1047–56 . 2010 . 20854421 . 3719988 . 10.1111/j.1474-9726.2010.00631.x .
4. Touzot F, Callebaut I, Soulier J, Gaillard L, Azerrad C, Durandy A, Fischer A, de Villartay JP, Revy P . Function of Apollo (SNM1B) at telomere highlighted by a splice variant identified in a patient with Hoyeraal-Hreidarsson syndrome . Proc. Natl. Acad. Sci. U.S.A. . 107 . 22 . 10097–102 . 2010 . 20479256 . 2890423 . 10.1073/pnas.0914918107 . 2010PNAS..10710097T . free .