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Cell Cycle Checkpoint Control in Response to DNA Damage

Award Number: R01GM053194
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/1995
PERIOD OF PERFORMANCE END DATE: 07/31/2014

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Cell Cycle Checkpoint Control in Response to DNA Damage - DESCRIPTION (provided by applicant): Cell cycle checkpoints ensure the integrity of the genome from one replicative cell cycle to the next. In the event of catastrophic damage to the genome, cells of multicellular eukaryotes can undergo apoptosis, presumably to eliminate them from the cell population and reduce the risk of propagating genetically unstable cells. Alternatively, cells may respond to DNA damage by undergoing a transient arrest of the cell cycle, which correlates with their ability to survive exposure to DNA damaging agents. This response requires the DNA damage checkpoint pathway; if compromised by mutation or drug treatment, cells will enter mitosis with damaged DNA and die. The fission yeast has been an extremely valuable system for identifying and characterizing components of the DNA damage checkpoint. Indeed, many proteins that are now known to function in the checkpoint pathway in mammalian cells were identified solely based on their sequence homology to proteins that were identified genetically and functionally in yeast. Thus, it is clear that the identification of proteins in yeast using the power of classical genetics is a valid and productive means of identifying and gaining insight into the function of mammalian counterparts. Experiments described in this proposal will continue to investigate the protein kinase Chk1, a key regulator of the checkpoint in eukaryotic cells. In addition, we will focus on a novel fission yeast protein, Msc1. Msc1 shares structural domain homology with mammalian RbBP2, a protein identified by virtue of its ability to bind the tumor suppressor protein Rb and with PLU-1, the product of a gene that is up regulated in breast cancer cells. Msc1 was cloned because it can compensate for the loss of function Chk1. The Msc1 protein is important for chromosome stability. Experiments described in this proposal aim to dissect the role of the Msc1 protein in fission yeast, to lay the groundwork for understanding the functions of the human homologues. When cells experience damage to their DNA, they delay cell cycle progression in order to repair the damage. Agents that damage DNA are used in therapy of cancer because they tend to preferentially kill cells that are rapidly dividing, a feature common to many types of cancer. Pathways that delay cell cycle progression are called checkpoint pathways and it is critical to understand how these pathways work, both to appreciate how DNA damage brings about cell death and to identify ways in which to enhance killing by chemotherapeutic agents. The fission yeast has been an extremely valuable system for identifying and characterizing components of the DNA damage checkpoint. Our studies make use of the excellent genetics of this organism to elucidate mechanisms that are universally important for governing cell division in the face of DNA damage.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2016 ( Subtotal = -$388 )
2016	2011	Rutgers, The State Univ Biomedical & Health Sciences	65 Davidson Road	Piscataway	NJ	08854	MIDDLESEX	USA	Biomedical Research and Research Training	001	18	1/29/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$20,618
2016	2011	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	089032688	MIDDLESEX	USA	Biomedical Research and Research Training	000	17	1/29/2016	NON-COMPETING CONTINUATION	$20,230
														Subtotal = -$388

Issue Date FY: 2013 ( Subtotal = $389 )
2013	2011	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	000	17	8/12/2013	NON-COMPETING CONTINUATION	-$20,230
2013	2011	Rutgers, The State Univ Biomedical & Health Sciences	65 Davidson Road	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Biomedical Research and Research Training	002	18	8/15/2013	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2013	2011	Rutgers, The State Univ Biomedical & HEALTH Sciences	65 Davidson Road	Piscataway	NJ	08554		USA	Biomedical Research and Research Training	001	18	8/13/2013	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$20,619
														Subtotal = $389

Issue Date FY: 2012 ( Subtotal = $0 )
2012	2011	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	000	17	8/20/2012	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2011 ( Subtotal = $377,819 )
2011	2011	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	000	17	7/29/2011	NON-COMPETING CONTINUATION	$377,819
														Subtotal = $377,819

Issue Date FY: 2010 ( Subtotal = $381,636 )
2010	2010	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	000	16	7/1/2010	NON-COMPETING CONTINUATION	$381,636
														Subtotal = $381,636

Issue Date FY: 2009 ( Subtotal = $385,491 )
2009	2009	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	000	15	6/19/2009	NON-COMPETING CONTINUATION	$385,491
2009	2009	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	001	15	7/3/2009	NON-COMPETING CONTINUATION	-$385,491
2009	2009	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	002	15	7/10/2009	NON-COMPETING CONTINUATION	$385,491
														Subtotal = $385,491

Issue Date FY: 2008 ( Subtotal = $381,405 )
2008	2008	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	000	14	7/14/2008	COMPETING CONTINUATION	$381,405
														Subtotal = $381,405

Issue Date FY: 2007 ( Subtotal = $437,018 )
2007	2007	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	000	13	7/30/2007	NON-COMPETING CONTINUATION	$388,912
2007	2007	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	001	13	8/1/2007	SUPPLEMENT FOR EXPANSION	$48,106
														Subtotal = $437,018

Issue Date FY: 2006 ( Subtotal = $390,974 )
2006	2006	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	000	12	7/12/2006	NON-COMPETING CONTINUATION	$390,974
														Subtotal = $390,974

Issue Date FY: 2005 ( Subtotal = $390,885 )
2005	2005	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	000	11	7/28/2005	NON-COMPETING CONTINUATION	$390,885
														Subtotal = $390,885

Issue Date FY: 2004 ( Subtotal = $434,428 )
2004	2004	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Biomedical Research and Research Training	000	10	6/21/2004	COMPETING CONTINUATION	$434,428
														Subtotal = $434,428

Issue Date FY: 2003 ( Subtotal = $346,161 )
2003	2003	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Genetics and Developmental Biology Research and Research Training	000	9	6/30/2003	NON-COMPETING CONTINUATION	$346,161
														Subtotal = $346,161

Issue Date FY: 2002 ( Subtotal = $298,368 )
2002	2002	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Genetics and Developmental Biology Research and Research Training	000	8	7/25/2002	NON-COMPETING CONTINUATION	$298,368
														Subtotal = $298,368

Issue Date FY: 2001 ( Subtotal = $257,072 )
2001	2001	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Genetics and Developmental Biology Research and Research Training	000	7	7/13/2001	NON-COMPETING CONTINUATION	$257,072
														Subtotal = $257,072

Issue Date FY: 2000 ( Subtotal = $352,929 )
2000	2000	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Genetics and Developmental Biology Research and Research Training	000	6	7/27/2000	COMPETING CONTINUATION	$352,929
														Subtotal = $352,929

Issue Date FY: 1999 ( Subtotal = $253,999 )
1999	1999	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Genetics and Developmental Biology Research and Research Training	000	5	7/16/1999	NON-COMPETING CONTINUATION	$253,999
														Subtotal = $253,999

Issue Date FY: 1998 ( Subtotal = $242,558 )
1998	1998	UMDNJ, ROBERT WOOD JOHNSON MED SCH	335 GEO ST LIBERTY PLAZA 4 FL	NEW BRUNSWICK	NJ	08903	MIDDLESEX	USA	Genetics and Developmental Biology Research and Research Training	000	4	11/6/1998	NON-COMPETING CONTINUATION	$242,558
														Subtotal = $242,558

Grand Total All Awards = $4,930,744

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Cell Cycle Checkpoint Control in Response to DNA Damage

Award Number: R01GM053194

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/01/1995

PERIOD OF PERFORMANCE END DATE: 07/31/2014

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