Structure-function analysis of ribonucleotide bypass by B family DNA replicases
Abstract
More than a million ribonucleotides may be incorporated into the mammalian nuclear genome during each round of DNA replication. When these ribonucleotides are not removed, they persist in the DNA template used for the next round of replication. Here we show that replicases stall when attempting to bypass ribonucleotides in DNA templates, with stalling increasing as the number of consecutive ribonucleotides increases from one to four. Structural analysis reveals that stalling is associated with displacement of a conserved tyrosine residue that is important for template strand interactions and with an unpreferred C2´-endo conformation for the ribose. Replication fork stalling during ribonucleotide bypass is likely to be relevant to both negative and positive consequences of ribonucleotides in DNA.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- October 2013
- DOI:
- 10.1073/pnas.1309119110
- Bibcode:
- 2013PNAS..11016802C