Suppression of homologous recombination by the Saccharomyces cerevisiae linker histone.
The basic unit of chromatin in eukaryotes is the nucleosome, comprising 146 bp of DNA wound around two copies of each of four core histones. Chromatin is further condensed by association with linker histones. Saccharomyces cerevisiae Hho1p has sequence homology to other known linker histones and interacts with nucleosomes in vitro. However, disruption of HHO1 results in no significant changes in the phenotypes examined thus far. Here, we show that Hho1p is inhibitory to DNA repair by homologous recombination (HR). We find Hho1p is abundant and associated with the genome, consistent with a global role in DNA repair. Furthermore, we establish that Hho1p is required for a full life span and propose that this is mechanistically linked to its role in HR. Finally, we show that Hho1p is inhibitory to the recombination-dependent mechanism of telomere maintenance. The role of linker histones in genome stability, aging, and tumorigenesis is discussed.
Downs
Jessica A
JA
The Wellcome Trust/Cancer Research UK Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, United Kingdom.
Kosmidou
Effie
E
Morgan
Alan
A
Jackson
Stephen P
SP
D001483:Base Sequence; D002470:Cell Survival / Q000187:drug effects; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D004260:DNA Repair; D004271:DNA, Fungal / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific / Q000494:pharmacology; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D006657:Histones / Q000235:genetics / Q000502:physiology*; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D009153:Mutagens / Q000494:pharmacology; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins; D016615:Telomere / Q000378:metabolism; D013696:Temperature
D002843:Chromatin; D004271:DNA, Fungal; D006657:Histones; D009153:Mutagens; D009707:Nucleosomes; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D008741:Methyl Methanesulfonate; C037725:SCEI protein, S cerevisiae; D015252:Deoxyribonucleases, Type II Site-Specific