The amino-terminal tails of histones H2A and H3 coordinate efficient base excision repair, DNA damage signaling and postreplication repair in Saccharomyces cerevisiae

Rithy Meas; Michael J Smerdon; John J Wyrick

doi:10.1093/nar/gkv372

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The amino-terminal tails of histones H2A and H3 coordinate efficient base excision repair, DNA damage signaling and postreplication repair in Saccharomyces cerevisiae

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The amino-terminal tails of histones H2A and H3 coordinate efficient base excision repair, DNA damage signaling and postreplication repair in Saccharomyces cerevisiae

Rithy Meas, Michael J Smerdon and John J Wyrick

Nucleic acids research, Vol.43(10), pp.4990-5001

05/26/2015

DOI: https://doi.org/10.1093/nar/gkv372

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https://hdl.handle.net/2376/112706

PMCID: PMC4446432

PMID: 25897129

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Abstract

Sequence Deletion

Signal Transduction

Histones - chemistry

Saccharomyces cerevisiae - genetics

DNA Replication

Saccharomyces cerevisiae Proteins - genetics

DNA-Binding Proteins - genetics

Saccharomyces cerevisiae - metabolism

Histones - genetics

DNA Repair

Saccharomyces cerevisiae Proteins - metabolism

Saccharomyces cerevisiae - enzymology

DNA Damage

Histones - metabolism

DNA Glycosylases - metabolism

Saccharomyces cerevisiae Proteins - chemistry

Histone amino-terminal tails (N-tails) are required for cellular resistance to DNA damaging agents; therefore, we examined the role of histone N-tails in regulating DNA damage response pathways in Saccharomyces cerevisiae. Combinatorial deletions reveal that the H2A and H3 N-tails are important for the removal of MMS-induced DNA lesions due to their role in regulating the basal and MMS-induced expression of DNA glycosylase Mag1. Furthermore, overexpression of Mag1 in a mutant lacking the H2A and H3 N-tails rescues base excision repair (BER) activity but not MMS sensitivity. We further show that the H3 N-tail functions in the Rad9/Rad53 DNA damage signaling pathway, but this function does not appear to be the primary cause of MMS sensitivity of the double tailless mutants. Instead, epistasis analyses demonstrate that the tailless H2A/H3 phenotypes are in the RAD18 epistasis group, which regulates postreplication repair. We observed increased levels of ubiquitylated PCNA and significantly lower mutation frequency in the tailless H2A/H3 mutant, indicating a defect in postreplication repair. In summary, our data identify novel roles of the histone H2A and H3 N-tails in (i) regulating the expression of a critical BER enzyme (Mag1), (ii) supporting efficient DNA damage signaling and (iii) facilitating postreplication repair.

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Title: The amino-terminal tails of histones H2A and H3 coordinate efficient base excision repair, DNA damage signaling and postreplication repair in Saccharomyces cerevisiae
Creators: Rithy Meas - School of Molecular Biosciences, Washington State University, Pullman, WA 99164-7520, USA
Michael J Smerdon - School of Molecular Biosciences, Washington State University, Pullman, WA 99164-7520, USA
John J Wyrick - School of Molecular Biosciences, Washington State University, Pullman, WA 99164-7520, USA jwyrick@vetmed.wsu.edu
Publication Details: Nucleic acids research, Vol.43(10), pp.4990-5001
Academic Unit: Molecular Biosciences, School of
Publisher: England
Grant note: R01 ES002614 / NIEHS NIH HHS ES002614 / NIEHS NIH HHS
Identifiers: 99900548200901842
Language: English
Resource Type: Journal article