Disease relevance of TOP2B

• NUP98 is fused to topoisomerase (DNA) IIbeta 180 kDa (TOP2B) in a patient with acute myeloid leukemia with a new t(3;11)(p24;p15) [1].

High impact information on TOP2B

• Dual-color fusion gene-specific FISH and reverse transcription-PCR analysis verified that NUP98 was indeed fused to TOP2B [1].
• We found that the promoter activity of this TOP2B fragment was constant throughout the cell cycle, in contrast to the activity of the proximal promoter of TOP2A which was low in resting cells and enhanced during proliferation [2].
• Our results suggest that the binding sites for NF-Y and Sp1 are critical for TOP2B transcription [2].
• Furthermore, partial religation by EDTA of TOP2B-induced breaks prevents neither the inhibition of DNA synthesis nor DNA degradation [3].
• We tested whether the oocyte could repair TOP2B-induced sperm DNA breaks and whether partial religation by EDTA would allow spermatozoa to fertilize the oocytes normally [3].

Biological context of TOP2B

• TOP2A and TOP2B contain 35 and 36 exons, respectively, and both genes contain a high proportion of class 0 introns [4].
• CONCLUSIONS: TOP2B encodes a type II topoisomerase, which is involved in DNA transcription, replication, recombination, and mitosis, and besides TOP1, represents the second NUP98 fusion partner gene that belongs to the topoisomerase gene family [1].
• A similar, TOP2B-mediated, chromatin fragmentation, which is reversible, followed by digestion of the DNA by an intracellular nuclease occurs in somatic cells during apoptosis [5].
• Haplotype analysis in a second family refined the interval to a 3.4-cM region that includes the candidate genes TOP2B and SLC4A7 [6].

Anatomical context of TOP2B

• These data are the first demonstration of an active TOP2B in spermatozoa, suggesting this inert chromatin may be more active than previously thought [5].

Other interactions of TOP2B

• TOP2A is approx. 30kb whereas TOP2B is at least 49kb [4].

Analytical, diagnostic and therapeutic context of TOP2B

• Mutational analyses of putative regulatory elements indicated that two inverted CCAAT boxes (ICBs) within this region were essential for TOP2B promoter activity and gel mobility-shift assays indicated these sites bound the transcription factor nuclear factor-Y (NF-Y) [2].

References