Yeast Nhp6A/B and mammalian Hmgb1 facilitate the maintenance of genome stability

Sabrina Giavara, Effie Kosmidou, M. Prakash Hande, Marco E. Bianchi, Alan Morgan, Fabrizio D'Adda Di Fagagna, Stephen P. Jackson

Research output: Contribution to journalArticlepeer-review

Abstract

Saccharomyces cerevisiae Nhp6A and Nhp6B are chromatin architectural factors that belong to the high-mobility group box (HMGB) superfamily and appear to be functionally related to mammalian Hmgb1 [1]. They bind to the minor groove of double-stranded DNA in a non-sequence-specific manner [2] and thereby influence chromatin structure [3]. Previous work has implicated these proteins in a variety of nuclear processes, including chromatin remodeling, DNA replication, transcription, and recombination [4-10]. Here, we show that Nhp6A/B loss leads to increased genomic instability, hypersensitivity to DNA-damaging agents, and shortened yeast cell life span that is associated with elevated levels of extrachromosomal rDNA circles. Furthermore, we show that hypersensitivity toward UV light does not appear to reflect a decreased capacity for DNA repair but instead correlates with higher levels of UV-induced thymine dimer adducts being formed in cells lacking Nhp6A/B. Likewise, we show that mouse fibroblasts lacking Hmgb1 display higher rates of damage after UV irradiation than wild-type controls and also exhibit pronounced chromosomal instability. Taken together, these data indicate that Nhp6A/B and Hmgb1 protect DNA from damaging agents and thus guard against the generation of genomic aberrations.

Original languageEnglish
Pages (from-to)68-72
Number of pages5
JournalCurrent Biology
Volume15
Issue number1
DOIs
Publication statusPublished - Jan 11 2005

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

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