Isodicentric Y Chromosomes and Sex Disorders as Byproducts of Homologous Recombination that Maintains Palindromes
Massive palindromes in the human Y chromosome harbor mirror-image gene pairs essential for spermatogenesis. During evolution, these gene pairs have been maintained by intrapalindrome, arm-to-arm recombination. The mechanism of intrapalindrome recombination and risk of harmful effects are unknown. We...
| Glavni autori: | , , , , , , , , , |
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| Format: | Članak |
| Jezik: | en_US |
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Elsevier
2015
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| Online pristup: | http://hdl.handle.net/1721.1/96285 https://orcid.org/0000-0001-9920-3411 |
| _version_ | 1826189396793098240 |
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| author | Lange, Julian Skaletsky, Helen van Daalen, Saskia K.M. Embry, Stephanie L. Korver, Cindy M. Brown, Laura G. Oates, Robert D. Silber, Sherman Repping, Sjoerd Page, David C |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Lange, Julian Skaletsky, Helen van Daalen, Saskia K.M. Embry, Stephanie L. Korver, Cindy M. Brown, Laura G. Oates, Robert D. Silber, Sherman Repping, Sjoerd Page, David C |
| author_sort | Lange, Julian |
| collection | MIT |
| description | Massive palindromes in the human Y chromosome harbor mirror-image gene pairs essential for spermatogenesis. During evolution, these gene pairs have been maintained by intrapalindrome, arm-to-arm recombination. The mechanism of intrapalindrome recombination and risk of harmful effects are unknown. We report 51 patients with isodicentric Y (idicY) chromosomes formed by homologous crossing over between opposing arms of palindromes on sister chromatids. These ectopic recombination events occur at nearly all Y-linked palindromes. Based on our findings, we propose that intrapalindrome sequence identity is maintained via noncrossover pathways of homologous recombination. DNA double-strand breaks that initiate these pathways can be alternatively resolved by crossing over between sister chromatids to form idicY chromosomes, with clinical consequences ranging from spermatogenic failure to sex reversal and Turner syndrome. Our observations imply that crossover and noncrossover pathways are active in nearly all Y-linked palindromes, exposing an Achilles' heel in the mechanism that preserves palindrome-borne genes. |
| first_indexed | 2024-09-23T08:14:03Z |
| format | Article |
| id | mit-1721.1/96285 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:14:03Z |
| publishDate | 2015 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/962852022-09-30T08:28:24Z Isodicentric Y Chromosomes and Sex Disorders as Byproducts of Homologous Recombination that Maintains Palindromes Lange, Julian Skaletsky, Helen van Daalen, Saskia K.M. Embry, Stephanie L. Korver, Cindy M. Brown, Laura G. Oates, Robert D. Silber, Sherman Repping, Sjoerd Page, David C Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Page, David C. Lange, Julian Skaletsky, Helen Brown, Laura G. Massive palindromes in the human Y chromosome harbor mirror-image gene pairs essential for spermatogenesis. During evolution, these gene pairs have been maintained by intrapalindrome, arm-to-arm recombination. The mechanism of intrapalindrome recombination and risk of harmful effects are unknown. We report 51 patients with isodicentric Y (idicY) chromosomes formed by homologous crossing over between opposing arms of palindromes on sister chromatids. These ectopic recombination events occur at nearly all Y-linked palindromes. Based on our findings, we propose that intrapalindrome sequence identity is maintained via noncrossover pathways of homologous recombination. DNA double-strand breaks that initiate these pathways can be alternatively resolved by crossing over between sister chromatids to form idicY chromosomes, with clinical consequences ranging from spermatogenic failure to sex reversal and Turner syndrome. Our observations imply that crossover and noncrossover pathways are active in nearly all Y-linked palindromes, exposing an Achilles' heel in the mechanism that preserves palindrome-borne genes. National Institutes of Health (U.S.) Howard Hughes Medical Institute Netherlands Organization for Scientific Research University of Amsterdam. Academic Medical Center Boehringer Ingelheim (Fellowship) 2015-03-31T17:31:00Z 2015-03-31T17:31:00Z 2009-09 2009-07 Article http://purl.org/eprint/type/JournalArticle 00928674 1097-4172 http://hdl.handle.net/1721.1/96285 Lange, Julian, Helen Skaletsky, Saskia K.M. van Daalen, Stephanie L. Embry, Cindy M. Korver, Laura G. Brown, Robert D. Oates, Sherman Silber, Sjoerd Repping, and David C. Page. “Isodicentric Y Chromosomes and Sex Disorders as Byproducts of Homologous Recombination That Maintains Palindromes.” Cell 138, no. 5 (September 2009): 855–869. © 2009 Elsevier Inc. https://orcid.org/0000-0001-9920-3411 en_US http://dx.doi.org/10.1016/j.cell.2009.07.042 Cell Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier |
| spellingShingle | Lange, Julian Skaletsky, Helen van Daalen, Saskia K.M. Embry, Stephanie L. Korver, Cindy M. Brown, Laura G. Oates, Robert D. Silber, Sherman Repping, Sjoerd Page, David C Isodicentric Y Chromosomes and Sex Disorders as Byproducts of Homologous Recombination that Maintains Palindromes |
| title | Isodicentric Y Chromosomes and Sex Disorders as Byproducts of Homologous Recombination that Maintains Palindromes |
| title_full | Isodicentric Y Chromosomes and Sex Disorders as Byproducts of Homologous Recombination that Maintains Palindromes |
| title_fullStr | Isodicentric Y Chromosomes and Sex Disorders as Byproducts of Homologous Recombination that Maintains Palindromes |
| title_full_unstemmed | Isodicentric Y Chromosomes and Sex Disorders as Byproducts of Homologous Recombination that Maintains Palindromes |
| title_short | Isodicentric Y Chromosomes and Sex Disorders as Byproducts of Homologous Recombination that Maintains Palindromes |
| title_sort | isodicentric y chromosomes and sex disorders as byproducts of homologous recombination that maintains palindromes |
| url | http://hdl.handle.net/1721.1/96285 https://orcid.org/0000-0001-9920-3411 |
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