Essential Roles Of RNA Polymerase II Transcription And DNA Damage Response Pathway In The Maintenance Of Centromere Chromatin Assembly
Funder
National Health and Medical Research Council
Funding Amount
$601,224.00
Summary
A centromere is a region of DNA typically found near the middle of a chromosome where two identical sister chromatids come in contact. It is involved in cell division as the point of attachment to the mitotic spindle. Defective centromeres can result in genome instability, infertility and development of cancers. This work involves a study into how the identity of a centromere is maintained and inherited after each cell division. This has significant implication in the understanding of cell growt ....A centromere is a region of DNA typically found near the middle of a chromosome where two identical sister chromatids come in contact. It is involved in cell division as the point of attachment to the mitotic spindle. Defective centromeres can result in genome instability, infertility and development of cancers. This work involves a study into how the identity of a centromere is maintained and inherited after each cell division. This has significant implication in the understanding of cell growth and cancer development.Read moreRead less
Epigenetic Regulation Of Telomere Chromatin And Genome Stability
Funder
National Health and Medical Research Council
Funding Amount
$633,447.00
Summary
Telomeres are structures at the end of the chromosomes that impact cell replication. 15% of cancers, called ALT cancers, show telomere instability, increased DNA damage and are frequently mutated for the ATRX gene. ALT cancers have poor prognosis, due to the limited understanding of ALT cancer activation. This study aims to create a model of ALT activation to uncover the mechanisms that control ALT tumourigenesis. This could lead to potential ALT-specific diagnostic and therapeutic tools.
Function Of ATRX, H3.3 And PML Nuclear Bodies In The Regulation Of Telomere Chromatin Integrity
Funder
National Health and Medical Research Council
Funding Amount
$434,652.00
Summary
The telomere is required for protecting chromosome ends. During cell division and development, telomeres lose their repeats, exposing the chromosome ends to damage. The consequences of this damage are disease, cancer, and aging. By contrast, embryonic stem cells (ES) continually renew their telomeres and do not stop growing. ES cells thereby provide a means to unravel the molecular mechanisms of indefinite telomere renewal. Here we propose a novel mechanism that operates to control continual tel ....The telomere is required for protecting chromosome ends. During cell division and development, telomeres lose their repeats, exposing the chromosome ends to damage. The consequences of this damage are disease, cancer, and aging. By contrast, embryonic stem cells (ES) continually renew their telomeres and do not stop growing. ES cells thereby provide a means to unravel the molecular mechanisms of indefinite telomere renewal. Here we propose a novel mechanism that operates to control continual telomere renewal in ES cells.Read moreRead less
Epigenetic Regulation Of Core Centromere CENP-A Chromatin Integrity
Funder
National Health and Medical Research Council
Funding Amount
$318,284.00
Summary
A centromere is a region of DNA typically found near the middle of a chromosome where two identical sister chromatids come in contact. It is involved in cell division as the point of attachment to the mitotic spindle. Defective centromeres can result in genome instability, infertility and development of cancers. This work involves a study into how the identity of a centromere is maintained and inherited after each cell division. This has significant implication in the understanding of cell growt ....A centromere is a region of DNA typically found near the middle of a chromosome where two identical sister chromatids come in contact. It is involved in cell division as the point of attachment to the mitotic spindle. Defective centromeres can result in genome instability, infertility and development of cancers. This work involves a study into how the identity of a centromere is maintained and inherited after each cell division. This has significant implication in the understanding of cell growth and cancer development.Read moreRead less
The Special Role Of Histone Variants In Regulating The Inheritance And 3-dimensional Organisation Of The Epigenome
Funder
National Health and Medical Research Council
Funding Amount
$962,716.00
Summary
It has been more than a decade since the human genome has been completely sequenced but how this genomic information is selectively utilized to direct gene expression that is unique to each of the 200 different cell types of the human body remains to be elucidated. We have new data to suggest that it is how our genome is packaged into a variety of different and dynamic 3-dimensional structures in a cell that determines cell type specific programs of gene expression
A New Paradigm For The Control Of Cellular Function: The Dynamic Reshaping Of The Epigenome By Histone Variants
Funder
National Health and Medical Research Council
Funding Amount
$672,735.00
Summary
Our DNA is packaged and partitioned into stable identities, chromosomes, which is critical for proper cell function and the inheritance of our genetic material from one cell generation to the next. Loss of chromosome integrity leads to cancer and therefore the cell must ensure that this does not happen. We have uncovered a new mechanism whereby different components of chromosomes can dynamically move from one location to another to ensure chromosomes remain stable when they are challenged.
H2A.Z Acetylation: Deregulation Of Enhancer Activity And 3D Chromatin In Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$859,350.00
Summary
DNA is not linear but packaged in the cell nucleus in a three-dimensional (3D) structure in such a way that distal regulatory regions can interact to control gene expression. Our new data suggests that a chemical modification of the histone variant H2A.Z plays a critical role in the formation of the 3D chromatin structure. This project is aimed to dissect the role of H2A.Z in prescribing 3D structure, which will provide a more precise understanding of gene deregulation in cancer.
A New Function For Histone Variants In The Tissue-specific Regulation Of Pre-mRNA Splicing
Funder
National Health and Medical Research Council
Funding Amount
$657,224.00
Summary
It is estimated that greater than 90% of human genes undergo alternative RNA splicing, which can explain how protein diversity is achieved with a limited number of genes. However, how alternative splicing patterns are established remains poorly understood but is an important question given that 15-50% of human disease mutations are associated with changes to the splicing patterns of RNA. We have uncovered a new splicing mechanism, which involves changing the way DNA is packaged in a cell.