Journal
GENOME RESEARCH
Volume 15, Issue 8, Pages 1079-1085Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gr.3970105
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The standard model of eukaryotic ribosomal RNA (rRNA) genes involves tandem arrays with hundreds of units in clusters, the nucleolus organizer regions [NORs). A first genomic overview for human cells is reported here for these regions, which have never been sequenced in their totality, by Using molecular combing. The rRNA-coding regions are examined by fluorescence oil single molecules of DNA with two specific probes that cover their entire length. The standard organization assumed for rDNA units is a transcribed region followed by a nontranscribed spacer. While we confirmed this arrangement in many cases, unorthodox patterns were also observed in normal individuals, with one-third of the rDNA Units rearranged to form apparently palindromic structures (noncanonical Units) independent of the age of the donors. In cells from individuals with a deficiency in the WRN RecQ helicase (Werner syndrome), the proportion of palindromes increased to one-half. These findings, supported by Southern blot analyses, show that rRNA genes are a mosaic of canonical and (presumably nonfunctional) palindromic Units that may be altered by factors associated with genomic instability and pathology.
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