Dna phd repair thesis

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Dna phd repair thesis

PhD thesis, University of Nottingham. Current evidence indicates that DNA damage response DDR is a highly complex process that involves various pathways working in an orchestrated and interwoven manner in response to different types of damage to DNA.

Although specific defects of DDR remain to be deciphered in cancer as a general, there is certainly an undeniable relationship between a particular dysfunction of DDR and the phenotype of tumour [1, 2].

It has been demonstrated that familial forms of breast and ovarian cancer are characterised by defects in one of the main mechanisms of DDR homologous recombination HR as a result of germline loss-of-function mutations in one of HR modifying genes, such as BRCA1 and BRCA2 [1, 3, 4].

Defects of genes involved in other DDR pathways are also associated with specific types of cancers; for instance hereditary non polyposis colorectal cancer HNPCC is strongly associated with specific mutations in the DNA mismatch repair pathway.

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Several previous studies have demonstrated that impaired DDR Dna phd repair thesis a fundamental role in the pathogenesis and behaviour of breast cancer BC. However, characterisation of this complex process, the expression and co-expression of the key proteins involved in the various DDR pathways and their prognostic significance in BC remain to be defined.

The common characteristics of global DDR are multiple genes induction directly associated with sensing and repair of DNA, arrest of cell cycle, and cell division inhibition.

As a result DDR process does not only include genes activation involved in damage sensing as well as repair but additionally genes involved in control of cell-cycle [5].

Despite the fact that DDR may possibly involve activation of several pathways such as SUMOylation SUMO [6, 7] and many genes are engaged in different overlapping mechanisms, each pathway is characterised by activation and expression of a unique set of genes.

This could allow discovering the active or aberrant pathway in a given tumour [1, 4, 5]. This study explores the hypothesis that investigation of alterations in the different pathways of DNA-DSB, may contribute to the characteristics of BC.

Dna phd repair thesis

Therefore, the aim was to perform a comprehensive profiling of key proteins involved in the different DNA-DSB repair pathways in the different molecular classes of BC.

This approach aims to address the inherent problems arising from the complexity of DDR mechanism in BC with the potential of discovering a key pathway that is active or inactive in specific forms of BC that can be helpful to identify DNA repair status in individual BC patients.

The study cohort comprises three BC groups: The expression of these proteins was assessed using the well-established immunohistochemical technique utilising tissue microarray technology.

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This study highlight the complexity of DDR related proteins and the overlap between different pathways involved in DDR. Major prognostic and predictive variables can be very important in choosing suitable treatment plans, identifying the risk of recurrence and classifying patients for clinical trials.

In addition to expression, subcellular localisation of DDR proteins appeared to be a major factor in their role. Particularly, HR repair markers but not NHEJ showed worse features of cytoplasmic location of expression, whereas nuclear expression was associated with more favourable features. Finally, the results of this study provide further evidence to support combined use of IHC with the parallel analytic capability of protein microarray RPPA to investigate protein alterations in human tumours.Are you interested in developing your own research project?

Discover the PhD projects we currently have available for Alshareeda, Alaa () Assessment of DNA-damage repair in breast cancer. PhD thesis, University of Nottingham. EPI Outbreak Investigation and Response (5) I&S/NW, QSR J. BASEMAN Provides an introduction to infectious disease outbreaks of both domestic and global significance.

Students learn about outbreak detection, investigation and response activities and methodologies through a combination of lecture.

Dna phd repair thesis

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Together, the results suggest that replication-associated topological changes involving the molecular DNA bender, Hmo1, set the stage for dedicated repair reactions that limit errors during.

Welcome to Chromatin Dynamics and DNA Repair Laboratory and Centre for Environmental Sciences and Engineering @ IIT Kanpur. Lab members Prem Anand Murugan PhD Student, (ashio-midori.com, Madurai Kamraj University ) [email protected] Sachin Deshpande ashio-midori.com -IIT Kanpur Thesis title:An alternate role for Mg2+ in DNA binding in mycobacterial LexA.

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