Chaperoning HMGA2 protein protects stalled replication forks in stem and cancer cells
Maintaining genome integrity requires the accurate and complete replication of chromosomal DNA. This is of the utmost importance for embryonic stem cells (ESCs), which differentiate into cells of all lineages, including germ cells. However, endogenous and exogenous factors frequently induce stalling...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2014
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| Online Access: | https://hdl.handle.net/10356/102195 http://hdl.handle.net/10220/18834 |
| _version_ | 1811696684233654272 |
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| author | Goodman, Steven D. Tjokro, Natalia O. Yu, Haojie Lim, Hong Hwa Sathiyanathan, Padmapriya Natarajan, Suchitra Chew, Tian Wei Klonisch, Thomas Surana, Uttam Dröge, Peter |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Goodman, Steven D. Tjokro, Natalia O. Yu, Haojie Lim, Hong Hwa Sathiyanathan, Padmapriya Natarajan, Suchitra Chew, Tian Wei Klonisch, Thomas Surana, Uttam Dröge, Peter |
| author_sort | Goodman, Steven D. |
| collection | NTU |
| description | Maintaining genome integrity requires the accurate and complete replication of chromosomal DNA. This is of the utmost importance for embryonic stem cells (ESCs), which differentiate into cells of all lineages, including germ cells. However, endogenous and exogenous factors frequently induce stalling of replication forks in every cell cycle, which can trigger mutations and chromosomal instabilities. We show here that the oncofetal, nonhistone chromatin factor HMGA2 equips cells with a highly effective first-line defense mechanism against endonucleolytic collapse of stalled forks. This fork-stabilizing function most likely employs scaffold formation at branched DNA via multiple DNA-binding domains. Moreover, HMGA2 works independently of other human factors in two heterologous cell systems to prevent DNA strand breaks. This fork chaperone function seemingly evolved to preserve ESC genome integrity. It is hijacked by tumor (stem) cells to also guard their genomes against DNA-damaging agents widely used to treat cancer patients. |
| first_indexed | 2024-10-01T07:43:16Z |
| format | Journal Article |
| id | ntu-10356/102195 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:43:16Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | ntu-10356/1021952023-02-28T17:03:00Z Chaperoning HMGA2 protein protects stalled replication forks in stem and cancer cells Goodman, Steven D. Tjokro, Natalia O. Yu, Haojie Lim, Hong Hwa Sathiyanathan, Padmapriya Natarajan, Suchitra Chew, Tian Wei Klonisch, Thomas Surana, Uttam Dröge, Peter School of Biological Sciences DRNTU::Science::Biological sciences Maintaining genome integrity requires the accurate and complete replication of chromosomal DNA. This is of the utmost importance for embryonic stem cells (ESCs), which differentiate into cells of all lineages, including germ cells. However, endogenous and exogenous factors frequently induce stalling of replication forks in every cell cycle, which can trigger mutations and chromosomal instabilities. We show here that the oncofetal, nonhistone chromatin factor HMGA2 equips cells with a highly effective first-line defense mechanism against endonucleolytic collapse of stalled forks. This fork-stabilizing function most likely employs scaffold formation at branched DNA via multiple DNA-binding domains. Moreover, HMGA2 works independently of other human factors in two heterologous cell systems to prevent DNA strand breaks. This fork chaperone function seemingly evolved to preserve ESC genome integrity. It is hijacked by tumor (stem) cells to also guard their genomes against DNA-damaging agents widely used to treat cancer patients. ASTAR (Agency for Sci., Tech. and Research, S’pore) ASTAR (Agency for Sci., Tech. and Research, S’pore) Published version 2014-02-19T03:10:10Z 2019-12-06T20:51:20Z 2014-02-19T03:10:10Z 2019-12-06T20:51:20Z 2014 2014 Journal Article Yu, H., Lim, H. H., Tjokro, N., Sathiyanathan, P., Natarajan, S., Chew, T. W., et al. (2014). Chaperoning HMGA2 protein protects stalled replication forks in stem and cancer cells. Cell reports, 6, 1-14. 2211-1247 https://hdl.handle.net/10356/102195 http://hdl.handle.net/10220/18834 10.1016/j.celrep.2014.01.014 en Cell reports © 2014 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited. application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences Goodman, Steven D. Tjokro, Natalia O. Yu, Haojie Lim, Hong Hwa Sathiyanathan, Padmapriya Natarajan, Suchitra Chew, Tian Wei Klonisch, Thomas Surana, Uttam Dröge, Peter Chaperoning HMGA2 protein protects stalled replication forks in stem and cancer cells |
| title | Chaperoning HMGA2 protein protects stalled replication forks in stem and cancer cells |
| title_full | Chaperoning HMGA2 protein protects stalled replication forks in stem and cancer cells |
| title_fullStr | Chaperoning HMGA2 protein protects stalled replication forks in stem and cancer cells |
| title_full_unstemmed | Chaperoning HMGA2 protein protects stalled replication forks in stem and cancer cells |
| title_short | Chaperoning HMGA2 protein protects stalled replication forks in stem and cancer cells |
| title_sort | chaperoning hmga2 protein protects stalled replication forks in stem and cancer cells |
| topic | DRNTU::Science::Biological sciences |
| url | https://hdl.handle.net/10356/102195 http://hdl.handle.net/10220/18834 |
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