[5mCCTCTCTCC]4: an i-motif tetramer with intercalated T*T pairs

Area of Science:

• Molecular Biology
• Biochemistry
• Structural Biology

Background:

• The i-motif is a four-stranded DNA structure formed by intercalated duplexes.
• Hemiprotonated cytosine-cytosine pairs (C*C+) stabilize the i-motif structure.
• Thymidine-thymidine pairs (T*T) are generally not accommodated in the i-motif's face-to-face orientation.

Purpose of the Study:

• To investigate the structural basis for the exclusion of T*T pairs in i-motif formation.
• To explore exceptions to the general rule regarding T*T pair accommodation in i-motif structures.
• To identify constraints influencing the formation of i-motif DNA.

Main Methods:

• Structural investigation of i-motif tetramers containing thymidines.
• Analysis of DNA sequences with potential to form i-motif structures.
• Characterization of base-pairing interactions within the i-motif.

Main Results:

• The tetramer of 5mCCTCTCTCC forms an exception to the rule.
• This sequence accommodates long-lived, face-to-face intercalated T5*T5 pairs.
• The structure reveals specific configurations that overcome typical T*T intercalation conflicts.

Conclusions:

• The findings provide insights into the origin of conflicts hindering T*T intercalation in i-motif structures.
• Specific DNA sequences can overcome steric and energetic constraints for T*T pair formation in i-motifs.
• This research clarifies general constraints influencing i-motif DNA formation.