TY  - JOUR
A1  - Kurahashi, Hiroki
A1  - Inagaki, Hidehito
A1  - Hosoba, Eriko
A1  - Kato, Takema
A1  - Ohye, Tamae
A1  - Kogo, Hiroshi
A1  - Emanuel, Beverly S.
T1  - Molecular cloning of a translocation breakpoint hotspot in 22q11
Y1  - 2007/04/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 461 
EP  - 469 
DO  - 10.1101/gr.5769507 
VL  - 17 
IS  - 4 
UR  - http://genome.cshlp.org/content/17/4/461.abstract 
N2  - It has been well documented that 22q11 contains one of the most rearrangement-prone sites in the human genome, where the breakpoints of a number of constitutional translocations cluster. This breakage-sensitive region is located within one of the remaining unclonable gaps from the human genome project, suggestive of a specific sequence recalcitrant to cloning. In this study, we cloned a part of this gap and identified a novel 595-bp palindromic AT-rich repeat (PATRR). To date we have identified three translocation-associated PATRRs. They have common characteristics: (1) they are AT-rich nearly perfect palindromes, which are several hundred base pairs in length; (2) they possess non-AT-rich regions at both ends of the PATRR; (3) they display another nearby AT-rich region on one side of the PATRR. All of these features imply a potential for DNA secondary structure. Sequence analysis of unrelated individuals indicates no major size polymorphism, but shows minor nucleotide polymorphisms among individuals and cis-morphisms between the proximal and distal arms. Breakpoint analysis of various translocations indicates that double-strand-breakage (DSB) occurs at the center of the palindrome, often accompanied by a small symmetric deletion at the center. The breakpoints share only a small number of identical nucleotides between partner chromosomes. Taken together, these features imply that the DSBs are repaired through nonhomologous end joining or single-strand annealing rather than a homologous recombination pathway. All of these results support a previously proposed paradigm that unusual DNA secondary structure plays a role in the mechanism by which palindrome-mediated translocations occur. 
ER  -