TY - JOUR
T1 - A DNA repair protein and histone methyltransferase interact to promote genome stability in the Caenorhabditis elegans germ line
AU - Yang, Bing
AU - Xu, Xia
AU - Russell, Logan
AU - Sullenberger, Matthew T.
AU - Yanowitz, Judith L.
AU - Maine, Eleanor M.
N1 - Funding Information:
This study was supported by NIH grants R01GM089818 and R15GM119029 to E.M.M., by Syracuse University funding to E.M.M., and by NIH grant R01GM104007 to J.L.Y. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank: Geraldine Seydoux for critical technical advice; Yini Li for assistance with the HU assays and Fig 9 illustrations; Priscilla van Wynsberghe for design and initial construction of the mosSCI met-2::gfp repair template; Sarah Hall, Yiqing Guo, Yini Li, Maria Ow, and other members of the Maine and Hall labs for intellectual input throughout the course of the study; and Katherine McJunkin for facilitating the final stage of this study. Some strains were obtained from the Caenorhabditis Genetics Center, which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440). Some strains were obtained from the National BioResource Project under the auspices of Shohei Mitani.
Publisher Copyright:
© 2019 Yang et al. http://creativecommons.org/licenses/by/4.0/.
PY - 2019/2
Y1 - 2019/2
N2 - Histone modifications regulate gene expression and chromosomal events, yet how histone-modifying enzymes are targeted is poorly understood. Here we report that a conserved DNA repair protein, SMRC-1, associates with MET-2, the C. elegans histone methyltransferase responsible for H3K9me1 and me2 deposition. We used molecular, genetic, and biochemical methods to investigate the biological role of SMRC-1 and to explore its relationship with MET-2. SMRC-1, like its mammalian ortholog SMARCAL1, provides protection from DNA replication stress. SMRC-1 limits accumulation of DNA damage and promotes germline and embryonic viability. MET-2 and SMRC-1 localize to mitotic and meiotic germline nuclei, and SMRC-1 promotes an increase in MET-2 abundance in mitotic germline nuclei upon replication stress. In the absence of SMRC-1, germline H3K9me2 generally decreases after multiple generations at high culture temperature. Genetic data are consistent with MET-2 and SMRC-1 functioning together to limit replication stress in the germ line and in parallel to promote other germline processes. We hypothesize that loss of SMRC-1 activity causes chronic replication stress, in part because of insufficient recruitment of MET-2 to nuclei.
AB - Histone modifications regulate gene expression and chromosomal events, yet how histone-modifying enzymes are targeted is poorly understood. Here we report that a conserved DNA repair protein, SMRC-1, associates with MET-2, the C. elegans histone methyltransferase responsible for H3K9me1 and me2 deposition. We used molecular, genetic, and biochemical methods to investigate the biological role of SMRC-1 and to explore its relationship with MET-2. SMRC-1, like its mammalian ortholog SMARCAL1, provides protection from DNA replication stress. SMRC-1 limits accumulation of DNA damage and promotes germline and embryonic viability. MET-2 and SMRC-1 localize to mitotic and meiotic germline nuclei, and SMRC-1 promotes an increase in MET-2 abundance in mitotic germline nuclei upon replication stress. In the absence of SMRC-1, germline H3K9me2 generally decreases after multiple generations at high culture temperature. Genetic data are consistent with MET-2 and SMRC-1 functioning together to limit replication stress in the germ line and in parallel to promote other germline processes. We hypothesize that loss of SMRC-1 activity causes chronic replication stress, in part because of insufficient recruitment of MET-2 to nuclei.
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U2 - 10.1371/journal.pgen.1007992
DO - 10.1371/journal.pgen.1007992
M3 - Article
C2 - 30794539
AN - SCOPUS:85062640026
SN - 1553-7390
VL - 15
JO - PLoS genetics
JF - PLoS genetics
IS - 2
M1 - e1007992
ER -