DCLRE1A explained
DNA cross-link repair 1A protein is a protein that in humans is encoded by the DCLRE1A gene.[1] [2] [3]
DNA interstrand cross-links prevent strand separation, thereby physically blocking transcription, replication, and segregation of DNA. DCLRE1A is one of several evolutionarily conserved genes involved in repair of interstrand cross-links (Dronkert et al., 2000).[supplied by OMIM]
Function
The protein DCLRE1A (DNA cross-link repair 1A) is also referred to as SNM1A (sensitive to nitrogen mustard 1A). DCLRE1A is a 5’ to 3’ exonuclease that forms a complex with the Cockayne syndrome B (CSB) protein. In this complex, CSB modulates the exonuclease activity of DCLRE1A and coordinates the efficient assembly of DCLRE1A to sites of DNA damage.[4] In human cells, this complex is recruited to DNA inter-strand cross-links, a form of DNA damage. The complex then participates in the repair of the cross-linked DNA. DCLRE1A protein is thought to be recruited by CSB to facilitate cross-link unhooking following incision 5’ to the cross-link by another complex, the ERCC1/XPF nuclease complex. Failure of the DCLRE1A/CSB complex to carry out its repair function may contribute to the degenerative pathologies and premature aging features of Cockayne syndrome.
Further reading
- Nagase T, Miyajima N, Tanaka A . Prediction of the coding sequences of unidentified human genes. III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of cDNA clones from human cell line KG-1 . DNA Res. . 2 . 1 . 37–43 . 1995 . 7788527 . 10.1093/dnares/2.1.37 . etal. free .
- Dronkert ML, de Wit J, Boeve M . Disruption of mouse SNM1 causes increased sensitivity to the DNA interstrand cross-linking agent mitomycin C . Mol. Cell. Biol. . 20 . 13 . 4553–61 . 2000 . 10848582 . 10.1128/MCB.20.13.4553-4561.2000 . 85844 . etal.
- Richie CT, Peterson C, Lu T . hSnm1 colocalizes and physically associates with 53BP1 before and after DNA damage . Mol. Cell. Biol. . 22 . 24 . 8635–47 . 2003 . 12446782 . 10.1128/MCB.22.24.8635-8647.2002 . 139863 . etal.
- 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 .
- Zhang X, Richie C, Legerski RJ . Translation of hSNM1 is mediated by an internal ribosome entry site that upregulates expression during mitosis . DNA Repair (Amst.) . 1 . 5 . 379–90 . 2003 . 12509242 . 10.1016/S1568-7864(02)00015-0 .
- Deloukas P, Earthrowl ME, Grafham DV . The DNA sequence and comparative analysis of human chromosome 10 . Nature . 429 . 6990 . 375–81 . 2004 . 15164054 . 10.1038/nature02462 . 2004Natur.429..375D . etal. free .
- 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.
- Akhter S, Richie CT, Deng JM . Deficiency in SNM1 abolishes an early mitotic checkpoint induced by spindle stress . Mol. Cell. Biol. . 24 . 23 . 10448–55 . 2005 . 15542852 . 10.1128/MCB.24.23.10448-10455.2004 . 529044 . 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.
Notes and References
- Demuth I, Digweed M . Genomic organization of a potential human DNA-crosslink repair gene, KIAA0086 . Mutat Res . 409 . 1 . 11–6 . Nov 1998 . 9806498 . 10.1016/s0921-8777(98)00037-8.
- Hejna J, Philip S, Ott J, Faulkner C, Moses R . The hSNM1 protein is a DNA 5'-exonuclease . Nucleic Acids Res . 35 . 18 . 6115–23 . Oct 2007 . 17804464 . 2094091 . 10.1093/nar/gkm530 .
- Web site: Entrez Gene: DCLRE1A DNA cross-link repair 1A (PSO2 homolog, S. cerevisiae).
- Iyama T, Lee SY, Berquist BR, Gileadi O, Bohr VA, Seidman MM, McHugh PJ, Wilson DM . CSB interacts with SNM1A and promotes DNA interstrand crosslink processing . Nucleic Acids Res. . 43 . 1 . 247–58 . 2015 . 25505141 . 4288174 . 10.1093/nar/gku1279 .