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Germline DNA replication timing shapes mammalian genome composition
Mammalian DNA replication is a highly organized and regulated process. Large, Mb-sized regions are replicated at defined times along S-phase. Replication Timing (RT) is thought to play a role in shaping the mammalian genome by affecting mutation rates. Previous analyses relied on somatic RT profiles...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6144785/ https://www.ncbi.nlm.nih.gov/pubmed/29986092 http://dx.doi.org/10.1093/nar/gky610 |
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author | Yehuda, Yishai Blumenfeld, Britny Mayorek, Nina Makedonski, Kirill Vardi, Oriya Cohen-Daniel, Leonor Mansour, Yousef Baror-Sebban, Shulamit Masika, Hagit Farago, Marganit Berger, Michael Carmi, Shai Buganim, Yosef Koren, Amnon Simon, Itamar |
author_facet | Yehuda, Yishai Blumenfeld, Britny Mayorek, Nina Makedonski, Kirill Vardi, Oriya Cohen-Daniel, Leonor Mansour, Yousef Baror-Sebban, Shulamit Masika, Hagit Farago, Marganit Berger, Michael Carmi, Shai Buganim, Yosef Koren, Amnon Simon, Itamar |
author_sort | Yehuda, Yishai |
collection | PubMed |
description | Mammalian DNA replication is a highly organized and regulated process. Large, Mb-sized regions are replicated at defined times along S-phase. Replication Timing (RT) is thought to play a role in shaping the mammalian genome by affecting mutation rates. Previous analyses relied on somatic RT profiles. However, only germline mutations are passed on to offspring and affect genomic composition. Therefore, germ cell RT information is necessary to evaluate the influences of RT on the mammalian genome. We adapted the RT mapping technique for limited amounts of cells, and measured RT from two stages in the mouse germline - primordial germ cells (PGCs) and spermatogonial stem cells (SSCs). RT in germline cells exhibited stronger correlations to both mutation rate and recombination hotspots density than those of RT in somatic tissues, emphasizing the importance of using correct tissues-of-origin for RT profiling. Germline RT maps exhibited stronger correlations to additional genetic features including GC-content, transposable elements (SINEs and LINEs), and gene density. GC content stratification and multiple regression analysis revealed independent contributions of RT to SINE, gene, mutation, and recombination hotspot densities. Together, our results establish a central role for RT in shaping multiple levels of mammalian genome composition. |
format | Online Article Text |
id | pubmed-6144785 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-61447852018-09-25 Germline DNA replication timing shapes mammalian genome composition Yehuda, Yishai Blumenfeld, Britny Mayorek, Nina Makedonski, Kirill Vardi, Oriya Cohen-Daniel, Leonor Mansour, Yousef Baror-Sebban, Shulamit Masika, Hagit Farago, Marganit Berger, Michael Carmi, Shai Buganim, Yosef Koren, Amnon Simon, Itamar Nucleic Acids Res Genome Integrity, Repair and Replication Mammalian DNA replication is a highly organized and regulated process. Large, Mb-sized regions are replicated at defined times along S-phase. Replication Timing (RT) is thought to play a role in shaping the mammalian genome by affecting mutation rates. Previous analyses relied on somatic RT profiles. However, only germline mutations are passed on to offspring and affect genomic composition. Therefore, germ cell RT information is necessary to evaluate the influences of RT on the mammalian genome. We adapted the RT mapping technique for limited amounts of cells, and measured RT from two stages in the mouse germline - primordial germ cells (PGCs) and spermatogonial stem cells (SSCs). RT in germline cells exhibited stronger correlations to both mutation rate and recombination hotspots density than those of RT in somatic tissues, emphasizing the importance of using correct tissues-of-origin for RT profiling. Germline RT maps exhibited stronger correlations to additional genetic features including GC-content, transposable elements (SINEs and LINEs), and gene density. GC content stratification and multiple regression analysis revealed independent contributions of RT to SINE, gene, mutation, and recombination hotspot densities. Together, our results establish a central role for RT in shaping multiple levels of mammalian genome composition. Oxford University Press 2018-09-19 2018-07-09 /pmc/articles/PMC6144785/ /pubmed/29986092 http://dx.doi.org/10.1093/nar/gky610 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Genome Integrity, Repair and Replication Yehuda, Yishai Blumenfeld, Britny Mayorek, Nina Makedonski, Kirill Vardi, Oriya Cohen-Daniel, Leonor Mansour, Yousef Baror-Sebban, Shulamit Masika, Hagit Farago, Marganit Berger, Michael Carmi, Shai Buganim, Yosef Koren, Amnon Simon, Itamar Germline DNA replication timing shapes mammalian genome composition |
title | Germline DNA replication timing shapes mammalian genome composition |
title_full | Germline DNA replication timing shapes mammalian genome composition |
title_fullStr | Germline DNA replication timing shapes mammalian genome composition |
title_full_unstemmed | Germline DNA replication timing shapes mammalian genome composition |
title_short | Germline DNA replication timing shapes mammalian genome composition |
title_sort | germline dna replication timing shapes mammalian genome composition |
topic | Genome Integrity, Repair and Replication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6144785/ https://www.ncbi.nlm.nih.gov/pubmed/29986092 http://dx.doi.org/10.1093/nar/gky610 |
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