Home LiteratureArticle Details
PMID: 17709383 Published · ppublish English Journal Article

A highly polymorphic meiotic recombination mouse hot spot exhibits incomplete repair.

Molecular and cellular biology ·Vol. 27 ·No. 20 ·2007-10-00 ·Pages 7053-62

Bois PR

Abstract

The recent mapping of recombination hot spots in the human genome has demonstrated that crossover is a nonrandom process that occurs at well-defined positions along chromosomes. However, the mechanisms that direct hot-spot turnover in complex mammalian genomes are poorly understood. Analyses of the human genome are impaired by the inability to genetically dissect and molecularly manipulate recombinogenic regions to test their roles in regulating hot spots. Here, using the BXD recombinant inbred strains as a crossover library, three new recombination hot spots have been identified on mouse chromosome 19. Analyses of a highly polymorphic recombination hot spot (HS22) revealed that approximately 4% of recombinant molecules display complex and incomplete repair with discontinuous conversion tracts, as well as persistent heteroduplex DNA at crossover sites in mature spermatozoa. Also, sequence analysis of the wild house mouse revealed instability at the center of this hot spot. This suggests that complete repair is not required for completion of mammalian meiosis, a scenario that leaves duplex DNA containing mismatches at crossover sites.

MeSH Terms
Animals Base Sequence Chromosomes, Mammalian DNA/chemistry,genetics,metabolism DNA Repair Female Humans Male Meiosis/physiology Mice Mice, Inbred C57BL Microsatellite Repeats Molecular Sequence Data Nucleic Acid Conformation Polymorphism, Genetic Recombination, Genetic Sequence Alignment Spermatozoa/physiology
Chemicals
DNA
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Bois Philippe R J
Department of Cancer Biology, Genome Plasticity Laboratory, The Scripps Research Institute, 5353 Parkside Drive, RE-1, Jupiter, FL 33458, USA. [email protected]
References (42)
42 references, click to expand
  1. Clustering of hypervariable minisatellites in the proterminal regions of human autosomes.
    Genomics. 1988 Nov;3(4):352-60 PMID: 3243550
  2. Absence of the TAP2 human recombination hotspot in chimpanzees.
    PLoS Biol. 2004 Jun;2(6):e155 PMID: 15208713
  3. Repeat unit sequence variation in minisatellites: a novel source of DNA polymorphism for studying variation and mutation by single molecule analysis.
    Cell. 1990 Feb 9;60(3):473-85 PMID: 2406022
  4. Repair of specific base pair mismatches formed during meiotic recombination in the yeast Saccharomyces cerevisiae.
    Mol Cell Biol. 1991 Feb;11(2):737-45 PMID: 1990280
  5. Detection of single and multiple polymorphic loci by synthetic tandem repeats of short oligonucleotides.
    Electrophoresis. 1991 Feb-Mar;12(2-3):134-40 PMID: 2040260
  6. Complex gene conversion events in germline mutation at human minisatellites.
    Nat Genet. 1994 Feb;6(2):136-45 PMID: 8162067
  7. Complex recombination events at the hypermutable minisatellite CEB1 (D2S90).
    EMBO J. 1994 Jul 1;13(13):3203-10 PMID: 8039512
  8. Interaction between mismatch repair and genetic recombination in Saccharomyces cerevisiae.
    Genetics. 1994 May;137(1):19-39 PMID: 8056309
  9. Regulation of pepsinogen gene expression in epithelial cells of vertebrate stomach during development.
    Int J Dev Biol. 1994 Jun;38(2):273-9 PMID: 7526882
  10. Influences of array size and homogeneity on minisatellite mutation.
    EMBO J. 1998 Jun 15;17(12):3495-502 PMID: 9628885
  11. High-resolution mapping of crossovers in human sperm defines a minisatellite-associated recombination hotspot.
    Mol Cell. 1998 Aug;2(2):267-73 PMID: 9734365
  12. Extremely complex repeat shuffling during germline mutation at human minisatellite B6.7.
    Hum Mol Genet. 1999 May;8(5):879-88 PMID: 10196378
  13. Human minisatellites, repeat DNA instability and meiotic recombination.
    Electrophoresis. 1999 Jun;20(8):1665-75 PMID: 10435430
  14. Minisatellite instability and germline mutation.
    Cell Mol Life Sci. 1999 Sep;55(12):1636-48 PMID: 10526579
  15. MLH1 and MSH2 promote the symmetry of double-strand break repair events at the HIS4 hotspot in Saccharomyces cerevisiae.
    Genetics. 2005 Mar;169(3):1291-303 PMID: 15654114
  16. The large loop repair and mismatch repair pathways of Saccharomyces cerevisiae act on distinct substrates during meiosis.
    Genetics. 2005 Jul;170(3):1033-43 PMID: 15879514
  17. Endonucleolytic processing of covalent protein-linked DNA double-strand breaks.
    Nature. 2005 Aug 18;436(7053):1053-7 PMID: 16107854
  18. The mammalian melastatin-related transient receptor potential cation channels: an overview.
    Pflugers Arch. 2005 Oct;451(1):204-11 PMID: 15895246
  19. A fine-scale map of recombination rates and hotspots across the human genome.
    Science. 2005 Oct 14;310(5746):321-4 PMID: 16224025
  20. Making crossovers during meiosis.
    Biochem Soc Trans. 2005 Dec;33(Pt 6):1451-5 PMID: 16246144
  21. A haplotype map of the human genome.
    Nature. 2005 Oct 27;437(7063):1299-320 PMID: 16255080
  22. Crossover and noncrossover pathways in mouse meiosis.
    Mol Cell. 2005 Nov 23;20(4):563-73 PMID: 16307920
  23. Variation in human meiotic recombination.
    Annu Rev Genomics Hum Genet. 2004;5:317-49 PMID: 15485352
  24. Recombinant-inbred strains. An aid to finding identity, linkage, and function of histocompatibility and other genes.
    Transplantation. 1971 Mar;11(3):325-7 PMID: 5558564
  25. A system of nomenclature for band patterns of mouse chromosomes.
    Chromosoma. 1973;41(2):145-58 PMID: 4120886
  26. Characterization of a panel of highly variable minisatellites cloned from human DNA.
    Ann Hum Genet. 1987 Oct;51(Pt 4):269-88 PMID: 3482146
  27. Clarifying the mechanics of DNA strand exchange in meiotic recombination.
    Nature. 2006 Jul 13;442(7099):153-8 PMID: 16838012
  28. Initiation of meiotic recombination by formation of DNA double-strand breaks: mechanism and regulation.
    Biochem Soc Trans. 2006 Aug;34(Pt 4):523-5 PMID: 16856850
  29. A high-resolution single nucleotide polymorphism genetic map of the mouse genome.
    PLoS Biol. 2006 Nov;4(12):e395 PMID: 17105354
  30. Cis- and trans-acting elements regulate the mouse Psmb9 meiotic recombination hotspot.
    PLoS Genet. 2007 Jun;3(6):e100 PMID: 17590084
  31. Homologous DNA exchanges in humans can be explained by the yeast double-strand break repair model: a study of 17p11.2 rearrangements associated with CMT1A and HNPP.
    Hum Mol Genet. 1999 Nov;8(12):2285-92 PMID: 10545609
  32. High resolution analysis of haplotype diversity and meiotic crossover in the human TAP2 recombination hotspot.
    Hum Mol Genet. 2000 Mar 22;9(5):725-33 PMID: 10749979
  33. Meiotic recombination and flanking marker exchange at the highly unstable human minisatellite CEB1 (D2S90).
    Am J Hum Genet. 2000 Aug;67(2):333-44 PMID: 10869237
  34. Heteroduplex rejection in yeast?
    Genetics. 2000 Apr;154(4):1913-6 PMID: 10950640
  35. Frequency of minisatellite repeat number changes at the MS205 locus in human sperm before and after cancer chemotherapy.
    Environ Mol Mutagen. 2000;36(2):134-45 PMID: 11013412
  36. Reciprocal crossover asymmetry and meiotic drive in a human recombination hot spot.
    Nat Genet. 2002 Jul;31(3):267-71 PMID: 12089523
  37. An initiation site for meiotic crossing-over and gene conversion in the mouse.
    Nat Genet. 2002 Oct;32(2):296-9 PMID: 12244318
  38. High-resolution sperm typing of meiotic recombination in the mouse MHC Ebeta gene.
    EMBO J. 2003 Mar 17;22(6):1389-97 PMID: 12628931
  39. Comparative linkage-disequilibrium analysis of the beta-globin hotspot in primates.
    Am J Hum Genet. 2003 Dec;73(6):1330-40 PMID: 14628290
  40. PLC-epsilon: a shared effector protein in Ras-, Rho-, and G alpha beta gamma-mediated signaling.
    Mol Interv. 2003 Aug;3(5):273-80 PMID: 14993441
  41. Where the crossovers are: recombination distributions in mammals.
    Nat Rev Genet. 2004 Jun;5(6):413-24 PMID: 15153994
  42. Heteroduplex DNA correction in Saccharomyces cerevisiae is mismatch specific and requires functional PMS genes.
    Mol Cell Biol. 1989 Oct;9(10):4432-40 PMID: 2685551
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
Published
2007-10-00
Epub
2007-00-20
Pages
7053-62
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC2168899
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]