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Cantor, Sharon

One or more keywords matched the following properties of Cantor, Sharon

Property	Value
overview	Sharon Cantor's Lab Website Hereditary Breast Cancer Research in our group is focused on understanding how cells normally function to maintain genomic integrity and suppress cancer. In particular, we focus on the hereditary breast and ovarian cancer genes, BRCA1, BRCA2 and FANCJ (also known as BACH1 or BRIP1). FANCJ was named the BRCA1 Associated C-terminal Helicase (BACH1) because of its direct interaction with the C-terminal BRCA1-BRCT repeats and its ability to unwind the strands of DNA in an energy-dependent reaction. Human genetic studies resulted in the identification of two early-onset breast cancer patients with germ-line sequence changes in the FANCJ coding region. When these sequence changes were studied in vitro, both mutations resulted in a defective FANCJ protein. Interestingly, the (P47A) mutant disrupted and the (M299I) mutant enhanced the enzyme activity implicating that too little or too much enzyme activity predisposes to disease. Similar to BRCA2, FANCJ is also mutated in the cancer prone syndrome, Fanconi anemia (FA). FA is a chromosomal instability syndrome characterized by cellular hypersensitivity to DNA crosslinking agents, such as cisplatin. FA is a multi-genetic disease with at least 13 complementation groups identified and referred to as FA-A through FA-N. BRCA2 is the FANCD1 gene mutated in the FA-D1 complementation group whereas FANCJ is mutated in the FA-J complementation group. So far, FA associated mutations in FANCJ appear to be enzyme inactivating or disrupt FANCJ expression. Research indicates that proteins functioning in the so-called, FA-BRCA pathway suppress cancer because of roles in preserving the integrity of the genome. The FA-BRCA proteins function to repair DNA lesions, such as DNA inter-strand crosslinks through several activities including the promotion of homologous recombination (HR). HR is a relatively error-free mechanism to repair DNA double strand breaks. In addition, the FA-BRCA pathway has roles in promoting DNA damage tolerance through translesion synthesis, a typically error-prone mechanism. By functioning together in large complexes, the FA-BRCA proteins can reverse toxic DNA crosslinks with minimal error generation and restart replication forks. The laboratory is interested in a range of repair-related topics including (i) the role of FANCJ in DNA repair, DNA damage tolerance, and checkpoint signaling and how these functions contribute to tumor suppression (ii) how FANCJ function is regulated by direct interactions with BRCA1 and MLH1, a mismatch repair protein, (iii) the relationship between FANCJ, BRCA1, and MLH1 in DNA crosslink repair, (iv) identifying novel FANCJ protein modifications or interacting partners that contribute to the function of FANCJ in the DNA damage response and (v) understanding the underlying defects associated with loss of function of proteins in the BRCA-FA pathway and whether these defects can be suppressed. The long-term objective of our research is to use our basic understanding of the FA-BRCA pathway to identify clinical applications in the treatment of FA-BRCA associated cancers or syndromes.
Post Docs	A post-doctoral position is available immediately to study the role of genes found in a genome-wide RNAi screen to regulate the cellular response to the chemotherapy agent, cisplatin. The goal is to determine whether these genes function as tumor suppressor and/or regulate the mechanism of DNA repair processing. The laboratory is interested in understanding the role of hereditary cancer genes of the BRCA-Fanconi anemia pathway in DNA damage repair and tumor suppression. We seek motivated candidates with a PhD and background in cancer cell biology. Experience in mouse cancer models is desirable. The exceptional training environment within the Department of Cancer Biology at UMASS Medical School offers a rigorous and interactive research environment covering several aspects of tumor biology. Applicants should have excellent communication skills, and ability to conduct research independently and as a team. To apply, please send your CV with bibliography, a brief description of research experience and contact information for at least two references via email.

Property

Value

overview

Sharon Cantor's Lab Website

Hereditary Breast Cancer

Research in our group is focused on understanding how cells normally function to maintain genomic integrity and suppress cancer. In particular, we focus on the hereditary breast and ovarian cancer genes, BRCA1, BRCA2 and FANCJ (also known as BACH1 or BRIP1). FANCJ was named the BRCA1 Associated C-terminal Helicase (BACH1) because of its direct interaction with the C-terminal BRCA1-BRCT repeats and its ability to unwind the strands of DNA in an energy-dependent reaction. Human genetic studies resulted in the identification of two early-onset breast cancer patients with germ-line sequence changes in the FANCJ coding region. When these sequence changes were studied in vitro, both mutations resulted in a defective FANCJ protein. Interestingly, the (P47A) mutant disrupted and the (M299I) mutant enhanced the enzyme activity implicating that too little or too much enzyme activity predisposes to disease.

Similar to BRCA2, FANCJ is also mutated in the cancer prone syndrome, Fanconi anemia (FA). FA is a chromosomal instability syndrome characterized by cellular hypersensitivity to DNA crosslinking agents, such as cisplatin. FA is a multi-genetic disease with at least 13 complementation groups identified and referred to as FA-A through FA-N. BRCA2 is the FANCD1 gene mutated in the FA-D1 complementation group whereas FANCJ is mutated in the FA-J complementation group. So far, FA associated mutations in FANCJ appear to be enzyme inactivating or disrupt FANCJ expression.

Research indicates that proteins functioning in the so-called, FA-BRCA pathway suppress cancer because of roles in preserving the integrity of the genome. The FA-BRCA proteins function to repair DNA lesions, such as DNA inter-strand crosslinks through several activities including the promotion of homologous recombination (HR). HR is a relatively error-free mechanism to repair DNA double strand breaks. In addition, the FA-BRCA pathway has roles in promoting DNA damage tolerance through translesion synthesis, a typically error-prone mechanism. By functioning together in large complexes, the FA-BRCA proteins can reverse toxic DNA crosslinks with minimal error generation and restart replication forks.

The laboratory is interested in a range of repair-related topics including (i) the role of FANCJ in DNA repair, DNA damage tolerance, and checkpoint signaling and how these functions contribute to tumor suppression (ii) how FANCJ function is regulated by direct interactions with BRCA1 and MLH1, a mismatch repair protein, (iii) the relationship between FANCJ, BRCA1, and MLH1 in DNA crosslink repair, (iv) identifying novel FANCJ protein modifications or interacting partners that contribute to the function of FANCJ in the DNA damage response and (v) understanding the underlying defects associated with loss of function of proteins in the BRCA-FA pathway and whether these defects can be suppressed.

The long-term objective of our research is to use our basic understanding of the FA-BRCA pathway to identify clinical applications in the treatment of FA-BRCA associated cancers or syndromes.

Post Docs

A post-doctoral position is available immediately to study the role of genes found in a genome-wide RNAi screen to regulate the cellular response to the chemotherapy agent, cisplatin. The goal is to determine whether these genes function as tumor suppressor and/or regulate the mechanism of DNA repair processing. The laboratory is interested in understanding the role of hereditary cancer genes of the BRCA-Fanconi anemia pathway in DNA damage repair and tumor suppression. We seek motivated candidates with a PhD and background in cancer cell biology. Experience in mouse cancer models is desirable. The exceptional training environment within the Department of Cancer Biology at UMASS Medical School offers a rigorous and interactive research environment covering several aspects of tumor biology. Applicants should have excellent communication skills, and ability to conduct research independently and as a team. To apply, please send your CV with bibliography, a brief description of research experience and contact information for at least two references via email.

One or more keywords matched the following items that are connected to Cantor, Sharon

Item Type	Name
Academic Article	Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells.
Academic Article	BRCA1, BRCA2, and Rad51 operate in a common DNA damage response pathway.
Academic Article	FANCJ (BACH1) helicase forms DNA damage inducible foci with replication protein A and interacts physically and functionally with the single-stranded DNA-binding protein.
Academic Article	BRCA-FA pathway as a target for anti-tumor drugs.
Academic Article	Assessing the link between BACH1/FANCJ and MLH1 in DNA crosslink repair.
Academic Article	FANCJ/BACH1 acetylation at lysine 1249 regulates the DNA damage response.
Academic Article	Multifactorial contributions to an acute DNA damage response by BRCA1/BARD1-containing complexes.
Academic Article	BACH1 is a DNA repair protein supporting BRCA1 damage response.
Academic Article	Targeting the FANCJ-BRCA1 interaction promotes a switch from recombination to poleta-dependent bypass.
Academic Article	Fanconi anemia group J helicase and MRE11 nuclease interact to facilitate the DNA damage response.
Concept	DNA Damage
Academic Article	FANCJ localization by mismatch repair is vital to maintain genomic integrity after UV irradiation.
Academic Article	Crosstalk between BRCA-Fanconi anemia and mismatch repair pathways prevents MSH2-dependent aberrant DNA damage responses.
Academic Article	What is wrong with Fanconi anemia cells?
Academic Article	Replication fork stability confers chemoresistance in BRCA-deficient cells.
Academic Article	Impairment of fetal hematopoietic stem cell function in the absence of Fancd2.
Academic Article	Opposing Roles of FANCJ and HLTF Protect Forks and Restrain Replication during Stress.
Academic Article	FANCJ compensates for RAP80 deficiency and suppresses genomic instability induced by interstrand cross-links.
Academic Article	Targeting translesion synthesis (TLS) to expose replication gaps, a unique cancer vulnerability.
Academic Article	Single-molecule imaging reveals replication fork coupled formation of G-quadruplex structures hinders local replication stress signaling.
Academic Article	Loss of nuclear DNA ligase III reverts PARP inhibitor resistance in BRCA1/53BP1 double-deficient cells by exposing ssDNA gaps.

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