TY - JOUR
T1 - Palindrome-mediated chromosomal translocations in humans
AU - Kurahashi, Hiroki
AU - Inagaki, Hidehito
AU - Ohye, Tamae
AU - Kogo, Hiroshi
AU - Kato, Takema
AU - Emanuel, Beverly S.
N1 - Funding Information:
The author wishes to thank Dr. T.H. Shaikh for providing materials, Dr. M. Taniguchi for helpful discussion, and Miss H. Kowa, K. Nagaoka, T. Mori, and E. Hosoba for technical assistance. These studies were supported by a grant-in-aid for Scientific Research, Genome, and 21st Century COE program from the Ministry of Education, Culture, Sports, Science, and Technology of Japan to H.K. (16390102). Support was also provided by grant from the National Institutes of Health to B.S.E. (CA39926).
PY - 2006/9/8
Y1 - 2006/9/8
N2 - Recently, it has emerged that palindrome-mediated genomic instability contributes to a diverse group of genomic rearrangements including translocations, deletions, and amplifications. One of the best studied examples is the recurrent t(11;22) constitutional translocation in humans that has been well documented to be mediated by palindromic AT-rich repeats (PATRRs) on chromosomes 11q23 and 22q11. De novo examples of the translocation are detected at a high frequency in sperm samples from normal healthy males, but not in lymphoblasts or fibroblasts. Cloned breakpoint sequences preferentially form a cruciform configuration in vitro. Analysis of the junction fragments implicates frequent double-strand-breaks (DSBs) at the center of both palindromic regions, followed by repair through the non-homologous end joining (NHEJ) pathway. We propose that the PATRR adopts a cruciform structure in male meiotic cells, creating genomic instability that leads to the recurrent translocation.
AB - Recently, it has emerged that palindrome-mediated genomic instability contributes to a diverse group of genomic rearrangements including translocations, deletions, and amplifications. One of the best studied examples is the recurrent t(11;22) constitutional translocation in humans that has been well documented to be mediated by palindromic AT-rich repeats (PATRRs) on chromosomes 11q23 and 22q11. De novo examples of the translocation are detected at a high frequency in sperm samples from normal healthy males, but not in lymphoblasts or fibroblasts. Cloned breakpoint sequences preferentially form a cruciform configuration in vitro. Analysis of the junction fragments implicates frequent double-strand-breaks (DSBs) at the center of both palindromic regions, followed by repair through the non-homologous end joining (NHEJ) pathway. We propose that the PATRR adopts a cruciform structure in male meiotic cells, creating genomic instability that leads to the recurrent translocation.
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U2 - 10.1016/j.dnarep.2006.05.035
DO - 10.1016/j.dnarep.2006.05.035
M3 - Article
C2 - 16829213
AN - SCOPUS:33747874030
SN - 1568-7864
VL - 5
SP - 1136
EP - 1145
JO - DNA Repair
JF - DNA Repair
IS - 9-10
ER -