Title: FoSTeS, MMBIR and NAHR at the human proximal Xp region and the mechanisms of human Xq isochromosome formation
Authors: Koumbaris, George ×
Hatzisevastou-Loukidou, Hariklia
Alexandrou, Angelos
Ioannides, Marios
Christodoulou, Christodoulos
Fitzgerald, Tomas
Rajan, Diana
Clayton, Stephen
Kitsiou-Tzeli, Sophia
Vermeesch, Joris
Skordis, Nicos
Antoniou, Pavlos
Kurg, Ants
Georgiou, Ioannis
Carter, Nigel P
Patsalis, Philippos C #
Issue Date: Feb-2011
Publisher: IRL Press
Series Title: Human Molecular Genetics vol:20 issue:10 pages:1925-1936
Abstract: The recently described DNA replication-based mechanisms of fork stalling and template switching (FoSTeS) and microhomology-mediated break-induced replication (MMBIR) were previously shown to catalyze complex exonic, genic and genomic rearrangements. By analyzing a large number of isochromosomes of the long arm of chromosome X (i(Xq)), using whole genome tiling path array comparative genomic hybridization (aCGH), ultra-high resolution targeted aCGH and sequencing, we provide evidence that the FoSTeS and MMBIR mechanisms can generate large-scale gross chromosomal rearrangements leading to the deletion and duplication of entire chromosome arms, thus suggesting an important role for DNA replication-based mechanisms in both the development of genomic disorders and cancer. Furthermore, we elucidate the mechanisms of dicentric i(Xq) (idic(Xq)) formation and show that most idic(Xq) chromosomes result from non-allelic homologous recombination (NAHR) between palindromic low copy repeats (LCRs) and highly homologous palindromic LINE elements. We also show that nonrecurrent-breakpoint idic(Xq) chromosomes have microhomology-associated breakpoint junctions and are likely catalyzed by microhomology-mediated replication-dependent recombination (MMRDR) mechanisms such as FoSTeS and MMBIR. Finally, we stress the role of the proximal Xp region as a chromosomal rearrangement hotspot.
ISSN: 0964-6906
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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