The Efficiency of Global Genome-Nucleotide Excision Repair is Linked to the Fraction of Open rRNA Gene Chromatin, in Yeast.

Abstract

The yeast rDNA locus is a suitable model to study nucleotide excision repair (NER) in chromatin. A portion of rRNA genes is transcribed and largely depleted of nucleosomes, the remaining genes are not transcribed and folded in nucleosomes. In G1-arrested cells, most rRNA genes do not have nucleosomes. TC-NER removes UV-induced DNA lesions from the transcribed strand of active genes. GG-NER is less efficient and removes DNA lesions from the nontranscribed strand of active genes and from the inactive genome. Different from mammalian cells, in yeast, the rRNA gene-transcribed strand is repaired by RNA polymerase-I-dependent TC-NER. The opposite nontranscribed strand is repaired faster than both strands of inactive rRNA genes. In log-phase cells, RNA polymerase-I are dislodged from the damaged transcribed strand and partially replaced by nucleosomes. Contrary to log-phase cells, in G1-phase cells few, if any, histones are deposited on the open rRNA genes during NER. In this study, we compared GG-NER efficiency in the rRNA gene coding region: without nucleosomes, partially loaded or wholly loaded with nucleosomes. The results indicate that in log-phase cells histones obstruct GG-NER, whereas in G1-phase cells GG-NER is as efficient as TC-NER.