title: Structural aspects of RecA-dependent homologous strand exchange involving human telomeric DNA.
abstract: Telomeric DNA sequences in human cells and those of other vertebrates consist of long d(TTAGGG) repeats. In somatic cells, telomeres shorten every cell division with shortening serving as a mitotic clock that counts cell divisions and ultimately results in cellular senescence. Telomere length is principally maintained by a ribonucleoprotein, telomerase. However, a non-negligible proportion of human cells use a recombination-based mechanism for telomere maintenance, termed alternative maintenance of telomeres (ALT). Although the molecular mechanism of ALT is not known, GT-rich sequences in prokaryotes and eukaryotes display high levels of recombination relative to those of non-GT-rich DNA. We show that human telomeric strand-exchange complexes mediated by Escherichia coli RecA protein differ from those formed with nontelomeric sequences. Moreover, telomeric strand-exchange intermediates, unlike those involving nontelomeric sequences, exhibit a tendency to form higher-order nucleoprotein structures. We propose that the strong DNA unwinding activity inherent in the assembly of the RecA strand-exchange complex promotes the formation of alternative DNA structures at human telomeric loci. Organization of these noncanonical structures into higher-order complexes involving multiple DNA duplexes could facilitate the search for homology on different DNA molecules and provide a framework for understanding recombination-dependent mechanisms of telomere maintenance.
authors.affiliation: Department of Molecular and Cell Biology, University of Texas at Dallas, Richardson, Texas 75083, USA.
authors.forename: Sima S
authors.initials: SS
authors.lastname: Zein
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Levene
mesh_terms: D019175:DNA Methylation; D004277:DNA, Single-Stranded / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D009692:Nucleic Acid Heteroduplexes / Q000737:chemistry / Q000378:metabolism; D010957:Plasmids; D011938:Rec A Recombinases / Q000737:chemistry* / Q000378:metabolism; D011995:Recombination, Genetic; D013463:Sulfuric Acid Esters / Q000737:chemistry; D020080:Tandem Repeat Sequences; D016615:Telomere / Q000201:enzymology* / Q000378:metabolism
chemical_list: D004277:DNA, Single-Stranded; D009692:Nucleic Acid Heteroduplexes; D013463:Sulfuric Acid Esters; D011938:Rec A Recombinases; C007482:dimethyl sulfate