Replisome function during replicative stress is modulated by histone h3 lysine 56 acetylation through Ctf4

Area of Science:

• * Molecular Biology
• * Genetics
• * Biochemistry

Background:

• * Histone H3 lysine 56 acetylation (H3K56ac) is crucial for genome stability in Saccharomyces cerevisiae, particularly under DNA replication stress.
• * The exact mechanisms by which H3K56ac maintains genome integrity during replication stress are not fully understood.

Purpose of the Study:

• * To elucidate the role of H3K56ac in genome stability during DNA replication stress.
• * To identify the specific replisome components and pathways involved in H3K56ac-mediated genome maintenance.

Main Methods:

• * Genetic analyses in Saccharomyces cerevisiae.
• * Investigation of replisome component interactions under replication stress.
• * Examination of the role of Ctf4 and its interaction with Mms22.

Main Results:

• * Absence of H3K56ac leads to deleterious effects of replisome components upon replication fork collapse.
• * H3K56ac uncouples the Cdc45-Mcm2-7-GINS helicase complex and DNA polymerases via Ctf4 during replicative stress.
• * The N-terminal domain of Ctf4, mediating interaction with Mms22, is essential for the H3K56ac pathway.

Conclusions:

• * Ctf4 is a key component of the H3K56ac pathway essential for genome stability under replication stress.
• * Replicative stress promotes the interaction between Ctf4 and Mms22, highlighting a novel regulatory mechanism.
• * This study provides mechanistic insights into H3K56ac's role in maintaining genome stability.