D loop

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Schematic representation of a D-loop; the double helix of the DNA is only partially shown.

A D-loop (synonym displacement loop of Engl. Displacement loop ) is a form of secondary structures of DNA . It occurs temporarily in DNA repair , telomeres, and in the DNA replication of mtDNA .

properties

The D-Loop consists of a double-stranded DNA and a single-stranded DNA with a sequence complementary to one of the two DNA strands. As a result of the incorporation of the third strand, one of the two DNA strands is displaced in sections.

DNA repair

In one form of DNA repair, repair through homologous recombination , the D-Loop forms a transition state. In bacteria, a D-loop is generated by RecA , which is then split into a single strand by a resolvase . In mammals, the proteins RPA (a single-strand-binding protein ) and Rad52 , which in turn binds Rad51 , are involved in the formation of the D-loop.

Telomeres

When the telomeres replicate, a lasso-like structure is formed at their end, which is called a T-loop and contains a D-loop. The T-loop protects the ends of the telomeres from degradation by exonucleases . In the T-loop, the third strand comes from a 3 'overhang at the end of the double-stranded DNA (dsDNA), which pushes upstream between the double strand and thus forms the lasso shape. Shelterin binds to the telomeres .

mtDNA

In mitochondrial DNA ( mtDNA ) the D-loop of about 660  bp (base pairs) is located downstream directly after the L-strand promoter (with about 440 bp). The D-loop is in the mtDNA control region . The L-strand promoter and D-loop form a region of the origin of replication of the mtDNA, which is known as the main control region and is approximately 1100 base pairs long. The D-loop is here permanently from dsDNA with a DNA extended RNA - Primer ( 7 S DNA formed).

Applications

Within the main control region of the mtDNA there are two hypervariable regions that can be determined in the course of creating a phylogenetic tree by DNA sequencing of the D-loop. In the hypervariable regions, the mutation rate is about 200 to 400 times higher than that of DNA from the cell nucleus . In addition to the sequencing of Y chromosomes , the sequencing of the D-loop is one of the most frequently used methods for determining the degree of relationship in humans.

Some mutations in the hypervariable region are associated with various tumors , including cervical cancer , breast cancer , stomach cancer , colon cancer , liver cancer , lung cancer, and kidney cancer . The mutations T16126C, T16224C and T16311C in the first hypervariable region are negative prognostic factors for acute lymphoblastic leukemia in children. The T16189C mutation is associated with coronary disease in some Central Europeans.

history

The D-Loop was first described in 1971 by H. Kasamatsu and colleagues.

Individual evidence

  1. ↑ Katharina Munk: Pocket textbook Biology: Genetics. Georg Thieme Verlag, 2010, ISBN 978-3-131-68621-3 ( limited preview in the Google book search).
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  3. ↑ T. Shibata, T. Nishinaka, T. Mikawa, H. Aihara, H. Kurumizaka, S. Yokoyama, Y. Ito: Homologous genetic recombination as an intrinsic dynamic property of a DNA structure induced by RecA / Rad51-family proteins: a possible advantage of DNA over RNA as genomic material. In: Proceedings of the National Academy of Sciences . Volume 98, Number 15, July 2001, pp. 8425-8432, doi : 10.1073 / pnas.111005198 , PMID 11459985 , PMC 37453 (free full text).
  4. ^ KA Bernstein, S. Gangloff, R. Rothstein: The RecQ DNA helicases in DNA repair. In: Annual review of genetics. Volume 44, 2010, pp. 393-417, doi : 10.1146 / annurev-genet-102209-163602 , PMID 21047263 , PMC 4038414 (free full text).
  5. ↑ JD Griffith, L. Comeau, S. Rosenfield, RM Stansel, A. Bianchi, H. Moss, T. de Lange: Mammalian telomeres end in a large duplex loop. In: Cell. Volume 97, Number 4, May 1999, pp. 503-514, PMID 10338214 .
  6. ^ CW Greider: Telomeres do D-loop-T-loop. In: Cell. Volume 97, Number 4, May 1999, pp. 419-422, PMID 10338204 .
  7. ^ Lalit M. Srivastava: Plant Growth and Development. Academic Press, 2002, ISBN 978-0-080-51403-1 , p. 87.
  8. ↑ Thomas D. Pollard: Cell Biology E-Book. Elsevier Health Sciences, 2016, ISBN 978-0-323-40002-2 , p. 120.
  9. ↑ a b c Rolf Knippers: Molecular Genetics. Georg Thieme Verlag, 2006, ISBN 978-3-134-77009-4 , p. 460 ( limited preview in Google book search).
  10. ↑ DD Chang, DA Clayton: Priming of human mitochondrial DNA replication occurs at the light-strand promoter. In: Proceedings of the National Academy of Sciences . Volume 82, Number 2, January 1985, pp. 351-355, PMID 2982153 , PMC 397036 (free full text).
  11. ^ Roberto Scatena: Advances in Mitochondrial Medicine. Springer Science & Business Media, 2012, ISBN 978-9-400-72869-1 , p. 42 ( limited preview in Google book search).
  12. ↑ TJ Nicholls, M. Minczuk: In D-loop: 40 years of mitochondrial 7S DNA. In: Experimental Gerontology . Volume 56, August 2014, pp. 175-181, doi : 10.1016 / j.exger.2014.03.027 , PMID 24709344 .
  13. ↑ A. Larizza, G. Pesole, A. Reyes, E. SBISA, C. Saccone: Lineage specificity of the evolutionary dynamics of the mtDNA D-loop region in rodents. In: Journal of molecular evolution. Volume 54, Number 2, February 2002, pp. 145-155, doi : 10.1007 / s00239-001-0063-4 , PMID 11821908 .
  14. ↑ a b c d H. Li, D. Liu, J. Lu, Y. Bai: Physiology and pathophysiology of mitochondrial DNA. In: Advances in Experimental Medicine and Biology . Volume 942, 2012, pp. 39-51, doi : 10.1007 / 978-94-007-2869-1_2 , PMID 22399417 , PMC 4706180 (free full text).
  15. ^ S. Kundu, SK Ghosh: Trend of different molecular markers in the last decades for studying human migrations. In: Genes. Volume 556, number 2, February 2015, pp. 81-90, doi : 10.1016 / j.gene.2014.12.023 , PMID 25510397 .
  16. ↑ H. Kasamatsu, DL Robberson, J. Vinograd: A novel closed-circular mitochondrial DNA with properties of a replicating intermediate. In: Proceedings of the National Academy of Sciences . Volume 68, Number 9, September 1971, pp. 2252-2257, PMID 5289384 , PMC 389395 (free full text).