PARP Activity Fine-tunes the DNA Replication Choreography of Chk1-depleted Cells期刊界 All Journals 搜尽天下杂志传播学术成果专业期刊搜索期刊信息化学术搜索

按检索

PARP Activity Fine-tunes the DNA Replication Choreography of Chk1-depleted Cells

Institution:	1. Department of Chemistry and the Center for Molecular Study of Condensed Soft Matter, Illinois Institute of Technology, Chicago, IL 60616, United States;2. Department of Physics and the Center for Molecular Study of Condensed Soft Matter, Illinois Institute of Technology, Chicago, IL 60616, United States;1. Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA;2. Faculty of Environmental and Life Sciences, Beijing University of Technology, Beijing 100124, China;3. Department of Biological Chemistry, University of Michigan, Ann Arbor, MI, 48109, USA;1. Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, United States;2. Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, United States;3. Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, United States;4. Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, United States;5. The Skaggs Institute of Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, United States;1. Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, United States;2. Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, United States;1. Department of Pharmaceutical Chemistry and Bioanalytics, Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Kurt-Mothes-Str. 3, Halle/Saale, Germany;2. Interdisciplinary Research Center HALOmem, Charles Tanford Protein Center, Martin Luther University Halle-Wittenberg, Kurt-Mothes-Str. 3a, Halle/Saale, Germany;3. Institute of Biochemistry and Biotechnology, Martin Luther University Halle-Wittenberg, Kurt-Mothes-Str. 3, Halle/Saale, Germany;4. Biozentrum, Martin Luther University Halle-Wittenberg, Weinbergweg 22, Halle/Saale, Germany;5. Department of Neuroscience, Division of Biochemistry, University of Oldenburg, 26111 Oldenburg, Germany;6. Center for Structural Mass Spectrometry, Martin Luther University Halle-Wittenberg, Kurt-Mothes-Str. 3, Halle/Saale, Germany

Abstract:	Checkpoint Kinase 1 (Chk1) prevents DNA damage by adjusting the replication choreography in the face of replication stress. Chk1 depletion provokes slow and asymmetrical fork movement, yet the signals governing such changes remain unclear. We sought to investigate whether poly(ADP-ribose) polymerases (PARPs), key players of the DNA damage response, intervene in the DNA replication of Chk1-depleted cells. We demonstrate that PARP inhibition selectively alleviates the reduced fork elongation rates, without relieving fork asymmetry in Chk1-depleted cells. While the contribution of PARPs to fork elongation is not unprecedented, we found that their role in Chk1-depleted cells extends beyond fork movement. PARP-dependent fork deceleration induced mild dormant origin firing upon Chk1 depletion, augmenting the global rates of DNA synthesis. Thus, we have identified PARPs as novel regulators of replication fork dynamics in Chk1-depleted cells.

Keywords:	checkpoint fork elongation origin firing replication barrier fork reversal Chk1"} {"#name":"keyword" "$":{"id":"k0035"} "$$":[{"#name":"text" "_":"Checkpoint kinase 1 PARP"} {"#name":"keyword" "$":{"id":"k0045"} "$$":[{"#name":"text" "_":"poly(ADP-ribose) polymerase DDR"} {"#name":"keyword" "$":{"id":"k0055"} "$$":[{"#name":"text" "_":"DNA damage response DSB"} {"#name":"keyword" "$":{"id":"k0065"} "$$":[{"#name":"text" "_":"double-strand break CDK"} {"#name":"keyword" "$":{"id":"k00651"} "$$":[{"#name":"text" "_":"cyclin-dependent kinase Polη"} {"#name":"keyword" "$":{"id":"k006570"} "$$":[{"#name":"text" "_":"DNA polymerase eta
本文献已被 ScienceDirect 等数据库收录！

设为首页 | 免责声明 | 关于勤云 | 加入收藏