Research Interests

1. Alternative DNA structures
2. Relation of DNA structures to instability of repeated DNA sequences
3. Interaction of poly(ADP-ribose) polymerase with DNA

In addition to the predominant right-handed double-helical DNA (B-DNA), alternative DNA structure, such as a cruciform containing duplex branches, left-handed Z-DNA or triple-helical DNA, can locally form in specific sequences. We work to understand the roles of these structures in major biological processes, transcription, replication, recombination and mutagenesis. The formation of alternative structures creates strong blocks for DNA and RNA polymerases, thereby blocking replication and down-regulating transcription. Cruciforms and intramolecular triple-helix also strongly bend DNA and bring their flanking sequences in close proximity which may facilitate transcriptional initiation and homologous recombination. Alternative DNA structures may be the targets of DNA repair mechanisms. One of the major current interests of my group is to understand how the formation of non-B-DNA structures contributes to the length instability of repeating (tri- and pentanucleotide) sequences, eventually leading to the development of neurodegenerative diseases. We have identified complex length-dependent triplex structures that may block normal replication and transcription of GAA•TCC repeats, easy DNA unpairing in ATTCT•AGAAT repeats that may provoke an unscheduled initiation of replication, and specific binding of the DNA damage recognition protein UvrA to the CTG•CAG repeat loop-outs which form during slipped-misalignment of repeating strands. Another actively pursued goal of my group is to elucidate the mechanisms of DNA interaction with poly(ADP-ribose) polymerase (PARP-1). PARP-1 plays “a break sensor” and other roles in repair of single- and double-strand breaks. It has been also implicated in transcriptional regulation. We have recently shown that one regulatory mechanism may include direct binding of PARP-1 to non-B-DNA structures that form in the promoter regions of the genes during chromatin remodeling.

Representative Publications
Soyfer VN, Potaman VN (1995) Triple-Helical Nucleic Acids. Springer-Verlag, New York, 360 pp.

Shlyakhtenko LS, Potaman VN, Sinden RR, Lyubchenko YL (1998) Structure and dynamics of supercoil-stabilized DNA cruciforms. J. Mol. Biol. 280: 61-72.

Oussatcheva EA, Hashem VI, Zou Y, Sinden RR, Potaman VN (2001) Involvement of the nucleotide excision repair protein UvrA in instability of CAG•CTG repeat sequences in Escherichia coli. J. Biol. Chem. 276: 30878-30884.

Soldatenkov VA, Chasovskikh S, Potaman VN, Trofimova I, Smulson ME, Dritschilo A (2002) Transcriptional repression by binding of poly(ADP-ribose) polymerase to promoter sequences. J. Biol. Chem. 277: 665-670.

Potaman VN, Bissler JJ, Hashem VI, Oussatcheva EA, Lu L, Shlyakhtenko LS, Lyubchenko YL, Matsuura T, Ashizawa T, Leffak M, Benham CJ, Sinden RR (2003) Unpaired structures in SCA10 (ATTCT)n•(AGAAT)n repeats. J. Mol. Biol. 326: 1095-1111.

My current PubMed record