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Archives of Industrial Biotechnology | Volume 2
May 14-15, 2018 | Montreal, Canada
World Yeast Congress
T
he protein
Swi6
in
Saccharomyces cerevisiae
is a cofactor
in two complexes that regulate the transcription of the
G1/S transition genes. It also ensures proper oxidative and
cell wall stress responses. Our previous study identified
SWI6
among genes linked to oversensitivity to radiomimetic
zeocin, i.e., genes important for surviving double-strand
break (DSB) stress. The
swi6
∆
/
swi6
∆
strain belongs to a
very limited group of knock-out strains with high sensitivity
to DSBs induced both chemically and by the
in vivo
overexpression of homing endonucleases. This group also
comprises strains lacking XRS2 or RAD52, whose products are
crucial in DSB repair. Moreover, one of our previous whole-
genome screens also identified the
swi6
∆
/
swi6
∆
strain as a
spontaneous mutator, indicating an important role of
Swi6
in
maintaining genome stability not only under genotoxic stress
but also during unperturbed cell growth. Results we have got
recently showed that
swi6
Δ mutants are genetically unstable
and the source of this instability is the replication block that
leads to double-strand break (DSB) formation. The cellular
pathway that enables the repair of replication-born DSBs
is the Rad51-dependent illegitimate recombination. Using
this repair pathway increases the chance to survive DNA
damage because it allows replication to resume. However, it
also leads to genome rearrangements, which subsequently
generate the division problems, which again leads to
poor growth and increased mortality. We also noticed the
differences between
swi6
Δ haploid and
swi6
Δ/swi6Δ diploid
yeast cells in the molecular outcomes of replication block,
which are not limited to different scenarios of replication
block resolution but include different adverse effects of
the absence of the
Swi6
protein in haploid vs. diploid cells
on mutation frequency in the forward mutation assay. The
overexpression of
SWI4
or PAB1 partially suppresses the
swi6
Δ cells oversensitivity to genotoxic agents. However,
only overexpression of one of them can overcome another
swi6
Δ mutation phenotypic hallmark; the DNA content
aberrations can be cured only by the overproduction of
SWI4
and not by PAB1.
Speaker Biography
Skoneczna A has completed her PhD from Institute of Biochemistry and Biophysics,
Polish Academy of Sciences, Poland. She is the Professor of Institute of Biochemistry
and Biophysics, Polish Academy of Sciences, Warsaw, Poland. She leads her group in
the Laboratory of Mutagenesis and DNA Repair. She has over 30 publications that have
been cited over 460 times, and her publication H-index is 12 and has been serving as
a reviewer of reputed journals, as well as in National Science Centre and The National
Centre for Research and Development.
e:
ada@ibb.waw.plLack of G1/S control in
swi6Δ
mutants destabilizes the genome of
S. cerevisiae
via replication stress-
induced DSBs and Rad51-mediated illegitimate recombination
Skoneczna Adrainna
IBB PAS, Poland