The roles of Tel1, Srs2 and Rad6 during meiotic DSB repair.

Meiosis is a cell division in which one diploid parent cell produces four haploid
daughter cells. Accurate alignment and segregation of homologous
chromosomes during metaphase is critical for a successful meiotic division and
viable gametes. Three concomitant events are required for a successful meiotic
division: chromosome pairing, synapsis and recombination. Recombination is
initiated by programmed induction of DNA double-strand breaks (DSBs).
Interchromosomal repair of meiotic DSBs can form a crossover leading to
genetic diversity by modifying linkage groups. Crossovers also tether the
homologous chromosomes and help resist the tension of the first meiotic
spindle. Controlled recombination is required for a successful meiotic division
and segregation, however, recombination has to be tightly regulated. This work
investigates the roles of Te11,Rad6 and Srs2 during meiotic homologous DSB
repair.
Tel1 is protein kinase required for initiating a signalling cascade in response to
many forms of DNA damage. Tel1 has also been proven to function during
meiosis and has been shown in some conditions to initiate a signalling cascade
after the initiation of meiotic DSBs. In this work Tel1 is shown to influence the
early stages of DSB repair during meiosis, however this is not in response to
the formation of Spo11-DSB.
Recombination ensures genetic variation and correct homologue alignment
during meiosis I therefore is extremely important and tightly controlled. Srs2 is
known to be a negative regulator of recombination and is important for normal
sporeulation and viability in yeast. Analysis of an experimental site specific DSB
(made by VDE) and at natural Spo11-DSBs indicates that in the absence of
Srs2 the rate of repair can be increased at Spo11-DSBs and decreased at the
VDE-DSB. One potential role for Srs2 during meiosis is to dismantle
recombination intermediates formed between the sister chromatids.
Rad6 is required for wild type amounts of Spo11-DSB formation. This work
investigated the VDE-DSB repair in the absence of Rad6, and discovered that
Rad6 has a role in the initiation of repair. Rad6 ubiquitinates histone H2B, and
further analyses suggest that this modification is required for repair at the VDEDSB.
Each of the genes studied is required for wild type repair of VDE-DSBs and
Spo11-DSBS, even though they come from widely different functional groups.
This illustrates the diversity of cellular pathways controlling the initiation and
regulation of meiotic recombination.