A role for the Saccharomyces cerevisiae Rtt109 histone acetyltransferase in R-loop homeostasis and associated genome...

Area of Science:

• Molecular Biology
• Genetics
• Chromatin Biology

Background:

• Genome stability is crucial and threatened by DNA-RNA hybrids (R-loops).
• R-loops impede DNA replication fork progression, causing stalling and breaks.
• Chromatin context significantly influences R-loop formation and resolution.

Purpose of the Study:

• Investigate the role of chromatin modifiers in R-loop metabolism.
• Identify specific factors involved in maintaining genome stability against R-loops.
• Elucidate the dual function of Rtt109 in R-loop management.

Main Methods:

• Screening of chromatin modifiers in Saccharomyces cerevisiae.
• Analysis of histone acetylation patterns (H3K14, H3K23, H3K56).
• Assessment of sensitivity to replication stress and THO-complex mutants.

Main Results:

• Rtt109 histone acetyltransferase plays a key role in R-loop metabolism.
• Rtt109 prevents DNA-RNA hybridization via H3K14 and H3K23 acetylation.
• Rtt109 facilitates DNA break repair through H3K14 and H3K56 acetylation.
• Rtt109 deficiency increases sensitivity to replication stress, especially with THO mutants.

Conclusions:

• Chromatin context influences both R-loop-associated DNA damage and its repair.
• Rtt109 is a critical regulator of genome stability in response to R-loops.
• Understanding Rtt109's function provides insights into R-loop-associated genetic instability.