genome-wide analyses of recombination prone regions predict role of dna structural motif in recombination全基因组分析复合易重组dna结构的主题区域预测作用.pdfVIP

Genome-Wide Analyses of Recombination Prone Regions Predict Role of DNA Structural Motif in Recombination Prithvi Mani1., Vinod Kumar Yadav1., Swapan Kumar Das3¤, Shantanu Chowdhury1,2* 1 G. N. Ramachandran Knowledge Centre for Genome Informatics, Institute of Genomics and Integrative Biology, CSIR, Delhi, India, 2 Proteomics and Structural Biology Unit, Institute of Genomics and Integrative Biology, CSIR, Delhi, India, 3 Functional Genomics Unit, Institute of Genomics and Integrative Biology, CSIR, Delhi, India Abstract HapMap findings reveal surprisingly asymmetric distribution of recombinogenic regions. Short recombinogenic regions (hotspots) are interspersed between large relatively non-recombinogenic regions. This raises the interesting possibility of DNA sequence and/or other cis- elements as determinants of recombination. We hypothesized the involvement of non-canonical sequences that can result in local non-B DNA structures and tested this using the G-quadruplex DNA as a model. G-quadruplex or G4 DNA is a unique form of four-stranded non-B DNA structure that engages certain G-rich sequences, presence of such motifs has been noted within telomeres. In support of this hypothesis, genome-wide computational analyses presented here reveal enrichment of potential G4 (PG4) DNA forming sequences within 25618 human hotspots relative to 9290 coldspots (p,0.0001). Furthermore, co-occurrence of PG4 DNA within several short sequence elements that are associated with recombinogenic regions was found to be significantly more than randomly expected. Interestingly, analyses of more than 50 DNA binding factors revealed that co-occurrence of PG4 DNA with target DNA binding sites of transcription factors c-Rel, NF- kappa B (p50 and p65) and Evi-1 was significantly enriched in recombination-prone regions. These observations support involvement of G4 DNA in reco