Differential repair of UV damage in rad mutants of Saccharomyces cerevisiae: a possible function of G2 arrest upon UV irradiation.

Abstract

After UV irradiation, the transcriptionally active MATa locus in Saccharomyces cerevisiae is preferentially repaired compared with the inactive HMLa locus. The effect of rad mutations from three different epistasis groups on differential repair was investigated. Three mutants, rad9, radl6, and rad24, were impaired in the removal of UV dimers from the inactive HMLa locus, whereas they had generally normal repair of the active MATa locus. Since RAD9 is necessary for G2 arrest after UV irradiation, we propose that the G2 stage plays a role in making the dimers accessible for repair, at least in the repressed HMLe locus.

Disparity of histone deacetylase inhibition on repair of radiation-induced DNA damage on euchromatin and constitutive heterochromatin compartments

“…In other words, not all chromatin should be considered equivalent in structure/function, including damage recognition/repair and this is reflected in our experiments examining phosphorylation of H2A.X at distinct regions of the genome. In particular, detection of gH2A.X was significantly lower on heterochromatic satellite 2 sequences and a-satellite repeats suggestive of reduced radiosensitivity, damage recognition or delayed DNA repair (Terleth et al, 1990;Livingstone-Zatchej et al, 2003). We can begin to interpret these results in the context of chromatin as a substrate for repair.…”

The Sir1 protein's association with a silenced chromosome domain

“…Both heterochromatic and silenced domains contain relatively hypoacetylated histones that, in combination with specialized nonhistone chromatin-associated proteins, form a repressive chromatin structure recalcitrant to a variety of activities requiring access to the chromosomal DNA. These specialized chromatin domains can transcriptionally repress genes contained within them, but they also can influence several other aspects of DNA metabolism including DNA replication, recombination, and repair and chromosome stability (Gottlieb and Esposito 1989;Terleth et al 1989Terleth et al , 1992Freeman-Cook et al 1999;Stevenson and Gottschling 1999;Henikoff 2000). Histone modifications and nonhistone proteins required for the assembly and maintenance of these specialized chromatin structures have been identified (Eissenberg et al 1995;Hendrich and Willard 1995;Pillus and Grunstein 1995), but the mechanisms that target and confine the formation of repressive chromatin to specific domains within the eukaryotic genome are unclear.…”

A UV-Responsive G2 Checkpoint in Rodent Cells

“…Not surprisingly, cells with mutations in genes affecting the G 1 or G 2 arrest pathway react adversely to treatment with DNA-damaging agents. Saccharomyces cerevisiae rad9 (and possibly rad17) mutants, which have defects in both G 1 and G 2 arrest in response to DNA damage (45,52), are more sensitive than wild-type cells to UV (50) and ionizing (52) radiation. The rad9 cells also have a higher frequency of spontaneous chromosome loss than wild-type cells (53).…”