Circular DNA in the human germline and its association with recombination
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Circular DNA in the human germline and its association with recombination. / Henriksen, Rasmus Amund; Jenjaroenpun, Piroon; Sjøstrøm, Ida Borup; Reveles Jensen, Kristian; Prada-Luengo, Iñigo; Wongsurawat, Thidathip; Nookaew, Intawat; Regenberg, Birgitte.
In: Molecular Cell, Vol. 82, No. 1, 2022, p. 209-217.e7.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Circular DNA in the human germline and its association with recombination
AU - Henriksen, Rasmus Amund
AU - Jenjaroenpun, Piroon
AU - Sjøstrøm, Ida Borup
AU - Reveles Jensen, Kristian
AU - Prada-Luengo, Iñigo
AU - Wongsurawat, Thidathip
AU - Nookaew, Intawat
AU - Regenberg, Birgitte
N1 - Publisher Copyright: © 2021 Elsevier Inc.
PY - 2022
Y1 - 2022
N2 - Extrachromosomal circular DNA (eccDNA) is common in somatic tissue, but its existence and effects in the human germline are unexplored. We used microscopy, long-read DNA sequencing, and new analytic methods to document thousands of eccDNAs from human sperm. EccDNAs derived from all genomic regions and mostly contained a single DNA fragment, although some consisted of multiple fragments. The generation of eccDNA inversely correlates with the meiotic recombination rate, and chromosomes with high coding-gene density and Alu element abundance form the least eccDNA. Analysis of insertions in human genomes further indicates that eccDNA can persist in the human germline when the circular molecules reinsert themselves into the chromosomes. Our results suggest that eccDNA has transient and permanent effects on the germline. They explain how differences in the physical and genetic map might arise and offer an explanation of how Alu elements coevolved with genes to protect genome integrity against deleterious mutations producing eccDNA.
AB - Extrachromosomal circular DNA (eccDNA) is common in somatic tissue, but its existence and effects in the human germline are unexplored. We used microscopy, long-read DNA sequencing, and new analytic methods to document thousands of eccDNAs from human sperm. EccDNAs derived from all genomic regions and mostly contained a single DNA fragment, although some consisted of multiple fragments. The generation of eccDNA inversely correlates with the meiotic recombination rate, and chromosomes with high coding-gene density and Alu element abundance form the least eccDNA. Analysis of insertions in human genomes further indicates that eccDNA can persist in the human germline when the circular molecules reinsert themselves into the chromosomes. Our results suggest that eccDNA has transient and permanent effects on the germline. They explain how differences in the physical and genetic map might arise and offer an explanation of how Alu elements coevolved with genes to protect genome integrity against deleterious mutations producing eccDNA.
KW - amplification
KW - complex rearrangements
KW - DM
KW - double minutes
KW - eccDNA
KW - evolution
KW - long-read sequencing
KW - structural variation
KW - translocation
U2 - 10.1016/j.molcel.2021.11.027
DO - 10.1016/j.molcel.2021.11.027
M3 - Journal article
C2 - 34951964
AN - SCOPUS:85121902550
VL - 82
SP - 209-217.e7
JO - Molecular Cell
JF - Molecular Cell
SN - 1097-2765
IS - 1
ER -
ID: 290116671