Isolation and sequencing of active origins of DNA replication by nascent strand capture and release (NSCR)

J Biol Methods. 2015;2(4):e33. doi: 10.14440/jbm.2015.92. Epub 2015 Dec 30.

Abstract

Nascent strand capture and release (NSCR) is a method for isolation of short nascent strands to identify origins of DNA replication. The protocol provided involves isolation of total DNA, denaturation, size fractionation on a sucrose gradient, 5'-biotinylation of the appropriate size nucleic acids, binding to a streptavidin coated magnetic beads, intensive washing, and specific release of only the RNA-containing chimeric nascent strand DNA using ribonuclease I (RNase I). The method has been applied to mammalian cells derived from proliferative tissues and cell culture but could be used for any system where DNA replication is primed by a small RNA resulting in chimeric RNA-DNA molecules.

Keywords: DNA replication; NSCR; SNS; origin mapping; ribonuclease I.