Article: TSPYL2 is important for G1 checkpoint maintenance upon DNA damage
| Title | TSPYL2 is important for G1 checkpoint maintenance upon DNA damage | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Tao, KP1 Fong, SW1 Lu, Z1 Ching, YP1 Chan, KW1 Chan, SY1 | ||||||
| Issue Date | 2011 | ||||||
| Publisher | Public Library of Science. The Journal's web site is located at http://www.plosone.org/home.action | ||||||
| Citation | Plos One, 2011, v. 6 n. 6 [How to Cite?] DOI: http://dx.doi.org/10.1371/journal.pone.0021602 | ||||||
| Abstract | Nucleosome assembly proteins play important roles in chromatin remodeling, which determines gene expression, cell proliferation and terminal differentiation. Testis specific protein, Y-encoded-like 2 (TSPYL2) is a nucleosome assembly protein expressed in neuronal precursors and mature neurons. Previous studies have shown that TSPYL2 binds cyclin B and inhibits cell proliferation in cultured cells suggesting a role in cell cycle regulation. To investigate the physiological significance of TSPYL2 in the control of cell cycle, we generated mice with targeted disruption of Tspyl2. These mutant mice appear grossly normal, have normal life span and do not exhibit increased tumor incidence. To define the role of TSPYL2 in DNA repair, checkpoint arrest and apoptosis, primary embryonic fibroblasts and thymocytes from Tspyl2 deficient mice were isolated and examined under unperturbed and stressed conditions. We show that mutant fibroblasts are impaired in G1 arrest under the situation of DNA damage induced by gamma irradiation. This is mainly attributed to the defective activation of p21 transcription despite proper p53 protein accumulation, suggesting that TSPYL2 is additionally required for p21 induction. TSPYL2 serves a biological role in maintaining the G1 checkpoint under stress condition. © 2011 Tao et al. | ||||||
| ISSN | 1932-6203 2011 Impact Factor: 4.092 2011 SCImago Journal Rankings: 0.519 | ||||||
| DOI | http://dx.doi.org/10.1371/journal.pone.0021602 | ||||||
| ISI Accession Number ID | WOS:000292092600061
Funding Information: The work described in this paper was substantially supported by a grant from the Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. HKU7323/03M and HKU2/02C) and partly by the Committee for Research and Conference Grants, The University of Hong Kong. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. | ||||||
| PubMed Central ID | PMC3124543 | ||||||
| References | References in Scopus |
| dc.contributor.author | Tao, KP | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Fong, SW | ||||||
| dc.contributor.author | Lu, Z | ||||||
| dc.contributor.author | Ching, YP | ||||||
| dc.contributor.author | Chan, KW | ||||||
| dc.contributor.author | Chan, SY | ||||||
| dc.date.accessioned | 2011-10-28T02:42:48Z | ||||||
| dc.date.available | 2011-10-28T02:42:48Z | ||||||
| dc.date.issued | 2011 | ||||||
| dc.description.abstract | Nucleosome assembly proteins play important roles in chromatin remodeling, which determines gene expression, cell proliferation and terminal differentiation. Testis specific protein, Y-encoded-like 2 (TSPYL2) is a nucleosome assembly protein expressed in neuronal precursors and mature neurons. Previous studies have shown that TSPYL2 binds cyclin B and inhibits cell proliferation in cultured cells suggesting a role in cell cycle regulation. To investigate the physiological significance of TSPYL2 in the control of cell cycle, we generated mice with targeted disruption of Tspyl2. These mutant mice appear grossly normal, have normal life span and do not exhibit increased tumor incidence. To define the role of TSPYL2 in DNA repair, checkpoint arrest and apoptosis, primary embryonic fibroblasts and thymocytes from Tspyl2 deficient mice were isolated and examined under unperturbed and stressed conditions. We show that mutant fibroblasts are impaired in G1 arrest under the situation of DNA damage induced by gamma irradiation. This is mainly attributed to the defective activation of p21 transcription despite proper p53 protein accumulation, suggesting that TSPYL2 is additionally required for p21 induction. TSPYL2 serves a biological role in maintaining the G1 checkpoint under stress condition. © 2011 Tao et al. | ||||||
| dc.description.nature | published_or_final_version | ||||||
| dc.identifier.citation | Plos One, 2011, v. 6 n. 6 [How to Cite?] DOI: http://dx.doi.org/10.1371/journal.pone.0021602 | ||||||
| dc.identifier.doi | http://dx.doi.org/10.1371/journal.pone.0021602 | ||||||
| dc.identifier.epage | e21602 | ||||||
| dc.identifier.hkuros | 196751 | ||||||
| dc.identifier.isi | WOS:000292092600061
Funding Information: The work described in this paper was substantially supported by a grant from the Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. HKU7323/03M and HKU2/02C) and partly by the Committee for Research and Conference Grants, The University of Hong Kong. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. | ||||||
| dc.identifier.issn | 1932-6203 2011 Impact Factor: 4.092 2011 SCImago Journal Rankings: 0.519 | ||||||
| dc.identifier.issue | 6 | ||||||
| dc.identifier.pmcid | PMC3124543 | ||||||
| dc.identifier.pmid | 21738728 | ||||||
| dc.identifier.scopus | eid_2-s2.0-79959598929 | ||||||
| dc.identifier.spage | e21602 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/142317 | ||||||
| dc.identifier.volume | 6 | ||||||
| dc.language | eng | ||||||
| dc.publisher | Public Library of Science. The Journal's web site is located at http://www.plosone.org/home.action | ||||||
| dc.publisher.place | United States | ||||||
| dc.relation.ispartof | PLoS ONE | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.rights | Creative Commons: Attribution 3.0 Hong Kong License | ||||||
| dc.subject.mesh | Apoptosis - genetics - physiology | ||||||
| dc.subject.mesh | Cell Cycle Proteins - genetics - metabolism | ||||||
| dc.subject.mesh | DNA Damage - genetics - physiology | ||||||
| dc.subject.mesh | G1 Phase - genetics - physiology | ||||||
| dc.subject.mesh | Immunohistochemistry | ||||||
| dc.title | TSPYL2 is important for G1 checkpoint maintenance upon DNA damage | ||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong Li Ka Shing Faculty of Medicine