@article{167f8b1467724f5eb53b88d3c2dc7349,
title = "HMCES Maintains Genome Integrity by Shielding Abasic Sites in Single-Strand DNA",
abstract = "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.",
keywords = "5-hydroxymethylcytosine, DNA repair, DNA replication, DNA-protein crosslink, HMCES, PCNA, REV1, SRAP, replication stress, translesion DNA synthesis",
author = "Mohni, {Kareem N.} and Wessel, {Sarah R.} and Runxiang Zhao and Wojciechowski, {Andrea C.} and Luzwick, {Jessica W.} and Hillary Layden and Eichman, {Brandt F.} and Thompson, {Petria S.} and Mehta, {Kavi P.M.} and David Cortez",
note = "Funding Information: We thank Drs. Karlene Cimprich, Maria Jasin, Jeremy Stark, John Pascal, and Alexander Drohat for providing reagents. We thank Dr. Carmelo Rizzo for the suggestion of looking at AP sites and Dr. Lisa Poole for help with RNA sequencing data analysis. We also thank Drs. Paul Modrich, James Berger, James Dewar, and Ian Macara for critical reading of the manuscript. This research was supported by grants to D.C. from the NIH (R01GM116616) and the Breast Cancer Research Foundation. K.N.M. was supported by Susan G. Komen fellowship PDF14302198 and 5T32CA009582. P.S.T. was supported by P01CA092584 and F30CA228242. S.R.W. was supported by F32GM126646. K.P.M.M. was supported by 5T32CA009582. Additional support came from the Vanderbilt-Ingram Cancer Center. Funding Information: We thank Drs. Karlene Cimprich, Maria Jasin, Jeremy Stark, John Pascal, and Alexander Drohat for providing reagents. We thank Dr. Carmelo Rizzo for the suggestion of looking at AP sites and Dr. Lisa Poole for help with RNA sequencing data analysis. We also thank Drs. Paul Modrich, James Berger, James Dewar, and Ian Macara for critical reading of the manuscript. This research was supported by grants to D.C. from the NIH ( R01GM116616 ) and the Breast Cancer Research Foundation . K.N.M. was supported by Susan G. Komen fellowship PDF14302198 and 5T32CA009582 . P.S.T. was supported by P01CA092584 and F30CA228242 . S.R.W. was supported by F32GM126646 . K.P.M.M. was supported by 5T32CA009582 . Additional support came from the Vanderbilt-Ingram Cancer Center . Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",
year = "2019",
month = jan,
day = "10",
doi = "10.1016/j.cell.2018.10.055",
language = "English (US)",
volume = "176",
pages = "144--153.e13",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "1-2",
}