Аннотация:It was analyzed nucleotide sequences of human genome, adjacent to the integration sites of human papilloma virus type 16 (HPV16). HPV16 is an etiologic factor at development of cervical cancer. The expression of viral genes can occur both with episomal and with integration forms. In the case of integrative form viral mRNA turns out to be adjacent at 3’-end with human cellular genomic nucleotide sequence, finishing with poly-A tail, that expects presence of poly(A)-site sequences downstream to 3’-end of integrated viral DNA. Using this feature the adjacenting virus-cellular expressed sequences was isolated, cloned and sequenced in Institute of Carcenogenesis, Cancer Research Center (Moscow). These sequences (INT markers) were used in our analysis.
Earlier we detected physical localization of five INT markers in genome of cervical carcinoma cells using RH-mapping method. The results of RH-mapping showed that virus DNA integrated in high-density gene regions of different human chromosomes. Using the BLASTN program significant homologies (98%-100%) with human genomic sequences and ESTs were showed for 12 INT markers. It was founded that in four cases the virus integrated in the sequences of hypothetical genes and in one case – in sequence similar to WASF2 gene.
We have undertaken the attempt to describe the sequences of four hypothetical genes (LOC161154, LOC151128, KIAA1808 and KIAA0887) and the sequence of similar to WASF2 gene. For these genes are construct exon-intron structure. For all genes are found start- (ATG) and stop-codons and poly-A sites. All exons of described by us genes are flanked the canonical splicing sites (AG…GT). It was determined promoter regions in 5’ regions of all genes and necessary binding sites for transcription factors are found. Searching of amino acid homologies and construction of the full local similarity maps determined the presupposed functions for two hypothetical proteins (KIAA1808 and KIAA0887).
