Protective Packaging for DNA: The Role of the PBAF and INO80 Chromatin Remodelling Complexes in Maintaining Genome Stability
Abstract
In eukaryotes, genomic DNA is packaged into the nucleus primarily by association with histone proteins to form chromatin. This structure, while necessary for compaction and chromosome segregation, is inhibitory to most processes that require access to DNA, such as transcription, replication and repair. For this reason, cells have two powerful mechanisms for manipulating the structure of chromatin; covalent modification of histones and ATP-dependent chromatin remodelling activities. Multiple chromatin modifying activities are involved in preventing genome instability by functioning to signal and repair damaged DNA, as well as to promote faithful chromosome segregation. The speaker and her team’s recent work has focused on two complexes: PBAF (also called SWI/SNF-B) and INO80. Both of these complexes contribute to cellular functions that promote and maintain genome stability, but by different mechanisms. Their aim is to investigate the molecular mechanisms underpinning these activities and to explore the potential interplay between these complexes in the cell. These studies will yield insights into how chromatin remodelling activities contribute to genome stability and prevent tumourigenesis.
About the speaker
Prof. Jessica Downs received her PhD in Zoology from the University of Cambridge in 1999. She stayed at Cambridge to pursue her postdoctoral studies at the Wellcome Trust/Cancer Research UK Gurdon Institute in 1999 – 2002. In 2002, she was awarded the Jenner Fellowship from the Lister Institute of Preventive Medicine, which she used to establish her own lab in the Biochemistry Department. In 2007, she moved to the University of Sussex as a Reader at the MRC Genome Damage and Stability Centre and is currently a Professor of Genome Stability in the Centre.
Prof. Downs is interested in understanding the dynamic interplay between chromatin and genome stability. Her research includes the study of chromatin structure and how it normally functions to maintain the integrity of the genome. She is also interested in understanding how changes to the structure and composition of chromatin can influence DNA damage responses. The aim of these strategies is to develop new insights about potential causes, treatments and biomarkers of cancer.
Prof. Downs is a member of the Biochemical Society and the founding organizer of the Genome Stability Network in UK. She has been the Associate Editor of DNA Repair since 2010 and in the editorial board of Molecular and Cellular Biology since 2011.
