|Fanconi anemia, complementation group M|
|Locus||Chr. 14 q21.3|
The protein encoded by this gene, FANCM displays DNA binding against fork structures and an ATPase activity associated with dissociation of DNA triplexes. It is believed that FANCM in conjunction with other Fanconi anemia-associated proteins repair DNA at stalled replication forks.
Recombination during meiosis is often initiated by a DNA double-strand break (DSB). During recombination, sections of DNA at the 5' ends of the break are cut away in a process called resection. In the strand invasion step that follows, an overhanging 3' end of the broken DNA molecule then "invades" the DNA of an homologous chromosome that is not broken forming a displacement loop (D-loop). After strand invasion, the further sequence of events may follow either of two main pathways leading to a crossover (CO) or a non-crossover (NCO) recombinant (see Genetic recombination and Homologous recombination). The pathway leading to a NCO is referred to as synthesis dependent strand annealing (SDSA).
In the plant Arabidopsis thaliana FANCM helicase antagonizes the formation of CO recombinants during meiosis, thus favoring NCO recombinants. The FANCM helicase is required for genome stability in humans and yeast, and is a major factor limiting meiotic CO formation in A. thaliana. A pathway involving another helicase, RECQ4A/B, also acts independently of FANCM to reduce CO recombination. These two pathways likely act by unwinding different joint molecule substrates (e.g. nascent versus extended D-loops; see Figure).
Only about 4% of DSBs in A. thaliana are repaired by CO recombination; the remaining 96% are likely repaired mainly by NCO recombination. Sequela-Arnaud et al. suggested that CO numbers are restricted because of the long-term costs of CO recombination, that is, the breaking up of favorable genetic combinations of alleles built up by past natural selection.
In the fission yeast Schizosaccharomyces pombe, FANCM helicase also directs NCO recombination during meiosis.
- Nagase T, Kikuno R, Nakayama M, Hirosawa M, Ohara O (August 2000). "Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 7 (4): 273–81. doi:10.1093/dnares/7.4.271. PMID 10997877.
- Meetei AR, Medhurst AL, Ling C; et al. (September 2005). "A human ortholog of archaeal DNA repair protein Hef is defective in Fanconi anemia complementation group M". Nat. Genet. 37 (9): 958–63. doi:10.1038/ng1626. PMC 2704909. PMID 16116422.
- Coulthard R, Deans AJ, Swuec P, Bowles M, Costa A, West SC, McDonald NQ (September 2013). "Architecture and DNA Recognition Elements of the Fanconi Anemia FANCM-FAAP24 Complex". Structure 21 (9): 1648–58. doi:10.1016/j.str.2013.07.006. PMID 23932590.
- Gari K, Décaillet C, Stasiak AZ, Stasiak A, Constantinou A (January 2008). "The Fanconi anemia protein FANCM can promote branch migration of Holliday junctions and replication forks". Mol. Cell 29 (1): 141–8. doi:10.1016/j.molcel.2007.11.032. PMID 18206976.
- Deans AJ, West SC (December 2009). "FANCM connects the genome instability disorders Bloom's Syndrome and Fanconi Anemia". Mol. Cell 36 (6): 943–53. doi:10.1016/j.molcel.2009.12.006. PMID 20064461.
- Meetei AR, Sechi S, Wallisch M, Yang D, Young MK, Joenje H, Hoatlin ME, Wang W (May 2003). "A multiprotein nuclear complex connects Fanconi anemia and Bloom syndrome". Mol. Cell. Biol. 23 (10): 3417–26. doi:10.1128/MCB.23.10.3417-3426.2003. PMC 164758. PMID 12724401.
- Séguéla-Arnaud M, Crismani W, Larchevêque C, Mazel J, Froger N, Choinard S, et al. (2015). "Multiple mechanisms limit meiotic crossovers: TOP3α and two BLM homologs antagonize crossovers in parallel to FANCM". Proc. Natl. Acad. Sci. U.S.A. 112 (15): 4713–8. doi:10.1073/pnas.1423107112. PMC 4403193. PMID 25825745.
- Crismani W, Girard C, Froger N, Pradillo M, Santos JL, Chelysheva L, et al. (2012). "FANCM limits meiotic crossovers". Science 336 (6088): 1588–90. doi:10.1126/science.1220381. PMID 22723424.
- Lorenz A, Osman F, Sun W, Nandi S, Steinacher R, Whitby MC (2012). "The fission yeast FANCM ortholog directs non-crossover recombination during meiosis". Science 336 (6088): 1585–8. doi:10.1126/science.1220111. PMC 3399777. PMID 22723423.
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