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The human transforming acidic coiled-coil 2 (TACC2) gene has been suggested recently to be a putative breast tumor suppressor. Now we can report the cloning of full length TACC2 cDNAs corresponding to the major isoforms expressed during development. The TACC2 gene is encoded by 23 exons, and spans 255 kb of chromosome 10q26. In breast cancer cell lines, TACC2 is expressed as a 120 kDa protein corresponding to the major transcript expressed in the mammary gland. Although only slight differences in the expression of TACC2 in normal versus breast tumors were observed, overexpression of TACC2 can alter the in vitro cellular dynamics of some breast cancer cell lines. Significantly, we demonstrate that TACC2 interacts with GAS41 and the SWI/SNF chromatin remodeling complex. This suggests that defects in TACC2 expression may affect gene regulation, thus contributing to the pathogenesis of some tumors.

Poly(ADP-ribosyl)ation of nuclear proteins plays a significant role in the maintenance of genomic DNA stability. To date, four poly(ADP-ribosyl)ating proteins have been identified in humans. We now report the full-length sequence, expression profile, and chromosomal localization of a novel gene, ADPRTL1, encoding an ADP-ribosyltransferase-like protein. The predicted open reading frame encodes a protein of 1724 amino acids with a molecular mass of 192.8 kDa. The protein contains a region showing homology to the catalytic domains of the nuclear-localized ADP-ribosyltransferase proteins (Adprt), two recently identified Adprt-like proteins (Adprtl2 and Adprtl3), and the telomere-associated protein tankyrase. Key amino acids known to be important for the activity of these enzymes are conserved within this region of the Adprtl1 protein, indicating that Adprtl1 is a functional poly(ADP-ribosyl)transferase. As has been noted for tankyrase, sequence analysis of the Adprtl1 protein suggests that it is not capable of binding DNA directly. Thus, the transferase activity of Adprtl1 may be activated by other factors such as protein–protein interaction mediated by the extensive carboxyl terminus. We have subsequently refined the location of the ADPRTL1 genomic locus to 13q11, close to the recently cloned ZNF198 gene.

We have recently identified a novel gene, TACC1 (transforming acidic coiled coil-containing gene 1), which is located close to FGFR1 within a region amplified in breast cancer on human chromosome 8p11. The coiled coil domain of this gene identified a series of cDNAs in the expressed sequence tag database, which suggested the existence of a family of TACC genes comprising at least three family members. We have now characterized the human and mouse TACC3 cDNAs, and demonstrate that this gene is upregulated in various cancer cell lines, and at Embryonic Day 15 in mice, suggesting that the TACC3 protein is involved in the control of cell growth and differentiation. The TACC3 gene maps telomeric to the FGFR3 gene in 4p16.3, close to a region disrupted by translocation breakpoints associated with multiple myeloma. Thus, TACC1, TACC2, and TACC3 map close to the corresponding FGFR1, FGFR2, and FGFR3 genes. The phylogenetic relationship among the three TACC genes is similar to that of the three FGFR family members. These relationships suggest that the FGFR and TACC genes arose from a physically linked ancestral gene pair. Subsequently, this gene pair has undergone two successive rounds of gene duplication to give rise to the three FGFR/TACC gene pairs on chromosomes 4, 8, and 10.

A panel of somatic cell hybrids carrying a defined set of rearrangements involving chromosome 13 has been used to assign 35 novel gene transcripts regionally. The positions of the chromosome 13 breakpoints in each somatic cell hybrid have previously been defined relative to the Genethon genetic linkage map. As a result, the position of each gene transcript has been determined relative to both the physical and the genetic linkage maps. Analysis of the distribution of these gene transcripts indicates a slight overrepresentation toward locations on the distal long arm of chromosome 13, with no localizations noted in the 13q22–q31 region. Seven of these novel gene transcripts and the gene encoding small ribonucleoprotein U6 have been mapped to YACs known to contain Genethon microsatellite markers, thereby providing further sublocalization relative to the genetic map. The positioning of these gene transcripts within the genetic and physical maps provides candidate genes for disease loci that are being mapped to the same intervals on the chromosome.