HMCES Maintains Genome Integrity by Shielding Abasic Sites in Single-Strand DNA.

Autor:	Mohni KN; Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA., Wessel SR; Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA., Zhao R; Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA., Wojciechowski AC; Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA., Luzwick JW; Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA., Layden H; Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA., Eichman BF; Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Department of Biological Sciences, Vanderbilt University, Nashville, TN 37232, USA., Thompson PS; Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA., Mehta KPM; Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA., Cortez D; Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. Electronic address: david.cortez@vanderbilt.edu.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2019 Jan 10; Vol. 176 (1-2), pp. 144-153.e13. Date of Electronic Publication: 2018 Dec 13.
DOI:	10.1016/j.cell.2018.10.055
Abstrakt:	Abasic sites are one of the most common DNA lesions. All known abasic site repair mechanisms operate only when the damage is in double-stranded DNA. Here, we report the discovery of 5-hydroxymethylcytosine (5hmC) binding, ESC-specific (HMCES) as a sensor of abasic sites in single-stranded DNA. HMCES acts at replication forks, binds PCNA and single-stranded DNA, and generates a DNA-protein crosslink to shield abasic sites from error-prone processing. This unusual HMCES DNA-protein crosslink intermediate is resolved by proteasome-mediated degradation. Acting as a suicide enzyme, HMCES prevents translesion DNA synthesis and the action of endonucleases that would otherwise generate mutations and double-strand breaks. HMCES is evolutionarily conserved in all domains of life, and its biochemical properties are shared with its E. coli ortholog. Thus, HMCES is an ancient DNA lesion recognition protein that preserves genome integrity by promoting error-free repair of abasic sites in single-stranded DNA. (Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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