DNA Recombination


DNA recombination plays an essential role both in generating genetic diversity during lymphocyte development and meiosis and in maintaining genome stability through DNA double‐strand break repair. In DNA recombination, two broad classes are commonly recognized: general recombination and site‐specific recombination.

Keywords: double‐strand break repair; nonhomologous end‐joining; homologous recombination; immunoglobulin gene rearrangement

Figure 1.

(DSB) repair by nonhomologous end‐joining. Notched lines represent inaccurate genetic information by either insertion or deletion of nucleotides at the DSB. DNA‐PKcs: DNA‐protein kinase catalytic subunit; XRCC4: X‐ray cross‐complementing 4.

Figure 2.

Double‐strand break (DSB) repair by homologous recombination. Bold lines in (d)–(f) represent newly synthesized DNA regions. RPA: replication protein A.

Figure 3.

Pathways involved in rearrangement of an immunoglobulin heavy chain locus. To simplify, only a fraction of genes are depicted as representatives of different segments: V: variable; D: diversity; and J: joining gene segments. Factors participating at each step are shown in blue. Gene conversion is also used in some species (see text). Note that both somatic hypermutation (SHM) and gene conversion can take place irrespective of a class switch recombination (CSR) event. Closed ovals represent switch regions located 5′ upstream of C genes. An asterisk represents a point mutation introduced into a VH region by somatic hypermutation. AID: activation‐induced cytidine deaminase; CSR: class switch recombination; HR: homologous recombination; NHEJ: nonhomologous end‐joining; SHM: somatic hypermutation.

Figure 4.

Mechanism of V(D)J recombination. An arrowhead in a rectangle represents a recombination signal sequence, consisting of a heptamer and a nonamer separated by 12 bp of spacer nucleotides. Factors participating in V(D)J recombination at each step are listed. Notched lines represent inserted extra nucleotides added at a junction between V and J segments. TdT: terminal deoxynucleoside transferase.

Figure 5.

Mechanism of class switch recombination (CSR) at an immunoglobulin heavy chain locus. The organization of immunoglobulin heavy chain constant‐region genes in humans is depicted. Factors participating in CSR at each step are listed on the right. CSR may take place successively, generating different isotypes. S region: switch region.



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Further Reading

Cromie GA, Connelly JC and Leach DR (2001) Recombination at double‐strand breaks and DNA ends: conserved mechanisms from phage to humans. Molecular Cell 8: 1163–1174.

Honjo T, Kinoshita K and Muramatsu M (2002) Molecular mechanism of class switch recombination: linkage with somatic hypermutation. Annual Review of Immunology 20: 165–196.

Khanna KK and Jackson SP (2001) DNA double‐strand breaks: signaling, repair and the cancer connection. Nature Genetics 27: 247–254.

Kuppers R and Dalla‐Favera R (2001) Mechanisms of chromosomal translocations in B cell lymphomas. Oncogene 20: 5580–5594.

Papavasiliou FN and Schatz DG (2002) Somatic hypermutation of immunoglobulin genes: merging mechanisms for genetic diversity. Cell 109: S35–S44.

Pierce AJ, Stark JM, Araujo FD, et al. (2001) Double‐strand breaks and tumorigenesis. Trends in Cell Biology 11: S52–S59.

Schlissel MS (2002) Does Artemis end the hunt for the hairpin‐opening activity in V(D)J recombination? Cell 109: 1–4.

Sonoda E, Takata M, Yamashita YM, Morrison C and Takeda S (2001) Homologous DNA recombination in vertebrate cells. Proceedings of the National Academy of Sciences of the United States of America 98: 8388–8394.

Thompson LH and Schild D (2001) Homologous recombinational repair of DNA ensures mammalian chromosome stability. Mutation Research 477: 131–153.

Web Links

BRCA1(breast cancer 1, early onset); Locus ID: 672. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=672

MRE11A(MRE11 meiotic recombination 11 homolog A(S. cerevisiae)); Locus ID: 4361. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=4361

NBS1(Nijmegen breakage syndrome 1(nibrin)); Locus ID: 4683. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=4683

BRCA1(breast cancer 1, early onset); MIM number: 113705. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?113705

MRE11A(MRE11 meiotic recombination 11 homolog A(S. cerevisiae)); MIM number: 600814. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/ dispmim?600814

NBS1(Nijmegen breakage syndrome 1(nibrin)); MIM number: 602667. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/ dispmim?602667

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How to Cite close
Takeda, Shunichi, and Yamazoe, Mitsuyoshi(Sep 2005) DNA Recombination. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005283]