Translin binding to DNA: recruitment through DNA ends and consequent conformational transitions.
The human translin protein binds a variety of sequences (chromosomal breakpoint consensus sequences, their sequence variants, as well as nonbreakpoint sequences such as simple AT and GC repeats) at nanomolar protein concentration when short single strands ( approximately 20-30mers) are used as DNA targets. The protein, which is known to exist as an octamer in its free state, undergoes a conformational transition upon binding to short single strands leading either to a compaction or to the dissociation of the oligomer. Moreover, the protein oligomers tend to aggregate into complexes that get progressively larger as the length of the single-stranded DNA target increases. The protein loads onto duplexes via the free ends of DNA, generating higher oligomeric complexes as a function of protein concentration. Interestingly, the conformation of DNA targets encased by translin oligomer is significantly altered such that the single strand is rendered hypersensitive to DNase I. Furthermore, the loading of translin oligomers leads to tighter clamping of duplex ends. All of these observations, taken together, suggest that translin is a bona fide binder of DNA ends, thereby subjecting the DNA to a conformation conducive for repair steps during translocation events. We discuss the results in the perspective of translin biology.
Sengupta
Kundan
K
Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Bombay 400 005, India.
Rao
Basuthkar J
BJ
D020816:Amino Acid Motifs / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D019457:Chromosome Breakage / Q000235:genetics; D016384:Consensus Sequence; D015342:DNA Probes / Q000737:chemistry; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D003850:Deoxyribonuclease I / Q000737:chemistry; D006801:Humans; D008956:Models, Chemical; D009690:Nucleic Acid Conformation; D009692:Nucleic Acid Heteroduplexes / Q000737:chemistry; D015345:Oligonucleotide Probes / Q000737:chemistry; D011485:Protein Binding / Q000235:genetics; D011487:Protein Conformation; D014178:Translocation, Genetic
D015342:DNA Probes; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D009692:Nucleic Acid Heteroduplexes; D015345:Oligonucleotide Probes; C095563:TSN protein, human; D003850:Deoxyribonuclease I