Human telomeres replicate using chromosome-specific, rather than universal, replication programs
Telomeric and adjacent subtelomeric heterochromatin pose significant challenges to the DNA replication machinery. Little is known about how replication progresses through these regions in human cells. Using single molecule analysis of replicated DNA (SMARD), we delineate the replication programs-i.e...
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| Veröffentlicht in: | The Journal of cell biology 2012-04, Vol.197 (2), p.253-266 |
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| container_title | The Journal of cell biology |
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| creator | Drosopoulos, William C Kosiyatrakul, Settapong T Yan, Zi Calderano, Simone G Schildkraut, Carl L |
| description | Telomeric and adjacent subtelomeric heterochromatin pose significant challenges to the DNA replication machinery. Little is known about how replication progresses through these regions in human cells. Using single molecule analysis of replicated DNA (SMARD), we delineate the replication programs-i.e., origin distribution, termination site location, and fork rate and direction-of specific telomeres/subtelomeres of individual human chromosomes in two embryonic stem (ES) cell lines and two primary somatic cell types. We observe that replication can initiate within human telomere repeats but was most frequently accomplished by replisomes originating in the subtelomere. No major delay or pausing in fork progression was detected that might lead to telomere/subtelomere fragility. In addition, telomeres from different chromosomes from the same cell type displayed chromosome-specific replication programs rather than a universal program. Importantly, although there was some variation in the replication program of the same telomere in different cell types, the basic features of the program of a specific chromosome end appear to be conserved. |
| doi_str_mv | 10.1083/jcb.201112083 |
| format | Article |
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Little is known about how replication progresses through these regions in human cells. Using single molecule analysis of replicated DNA (SMARD), we delineate the replication programs-i.e., origin distribution, termination site location, and fork rate and direction-of specific telomeres/subtelomeres of individual human chromosomes in two embryonic stem (ES) cell lines and two primary somatic cell types. We observe that replication can initiate within human telomere repeats but was most frequently accomplished by replisomes originating in the subtelomere. No major delay or pausing in fork progression was detected that might lead to telomere/subtelomere fragility. In addition, telomeres from different chromosomes from the same cell type displayed chromosome-specific replication programs rather than a universal program. 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Importantly, although there was some variation in the replication program of the same telomere in different cell types, the basic features of the program of a specific chromosome end appear to be conserved.</description><subject>Cell Line, Tumor</subject><subject>Chromatin</subject><subject>Chromosomes</subject><subject>Chromosomes, Human - metabolism</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA - metabolism</subject><subject>DNA Replication - physiology</subject><subject>Embryonic Stem Cells - metabolism</subject><subject>HeLa Cells</subject><subject>Heterochromatin</subject><subject>Humans</subject><subject>Stem cells</subject><subject>Telomere - metabolism</subject><issn>0021-9525</issn><issn>1540-8140</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc2LFDEQxYMo7rh69CoNXjxsr1X56EkuwrKoKyx40XPMpCszGbo7bdK94H9vZNdBPXkqivrVo149xl4iXCJo8fbod5ccEJHX7hHboJLQapTwmG0AOLZGcXXGnpVyBAC5leIpO-NcgVYIG_btZh3d1Cw0pJEylSbTPETvFmrWEqd94w85janUaVtm8jFEf9FktxwoN8uhrq5TvKNc3HBx2o1pauac9tmN5Tl7EtxQ6MVDPWdfP7z_cn3T3n7--On66rb1UsqlDcKYamDnw9b1He28DApl6OS2MxSCMhI6rY3ywTsHwoWOQGEveN_1oLcgztm7e9153Y3Ue5qW7AY75zi6_MMmF-3fkyke7D7dWSG4FlpUgTcPAjl9X6ksdozF0zC4idJaLEL9sJSGm_9AgStEbbCir_9Bj2nNU_1EpRAFgNaqUu095XMqJVM43Y1gf8Vsa8z2FHPlX_1p9kT_zlX8BM1RpJA</recordid><startdate>20120416</startdate><enddate>20120416</enddate><creator>Drosopoulos, William C</creator><creator>Kosiyatrakul, Settapong T</creator><creator>Yan, Zi</creator><creator>Calderano, Simone G</creator><creator>Schildkraut, Carl L</creator><general>Rockefeller University Press</general><general>The Rockefeller University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20120416</creationdate><title>Human telomeres replicate using chromosome-specific, rather than universal, replication programs</title><author>Drosopoulos, William C ; 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Little is known about how replication progresses through these regions in human cells. Using single molecule analysis of replicated DNA (SMARD), we delineate the replication programs-i.e., origin distribution, termination site location, and fork rate and direction-of specific telomeres/subtelomeres of individual human chromosomes in two embryonic stem (ES) cell lines and two primary somatic cell types. We observe that replication can initiate within human telomere repeats but was most frequently accomplished by replisomes originating in the subtelomere. No major delay or pausing in fork progression was detected that might lead to telomere/subtelomere fragility. In addition, telomeres from different chromosomes from the same cell type displayed chromosome-specific replication programs rather than a universal program. 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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Cell Line, Tumor Chromatin Chromosomes Chromosomes, Human - metabolism Deoxyribonucleic acid DNA DNA - metabolism DNA Replication - physiology Embryonic Stem Cells - metabolism HeLa Cells Heterochromatin Humans Stem cells Telomere - metabolism |
| title | Human telomeres replicate using chromosome-specific, rather than universal, replication programs |
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