Dr Aga Gambus

Dr Aga Gambus

Institute of Cancer and Genomic Sciences
Senior Lecturer, MRC Career Development and Lister Fellow

Contact details

Chromosomal Replication Laboratory
Institute of Cancer and Genomic Sciences
University of Birmingham
B15 2TT

Aga has moved to Cancer Sciences in 2011 to start her independent research. She was awarded MRC Career Development Award and Birmingham Fellowship supporting her research. In 2015 Aga was awarded Lister Institute Research Award and BACR/AstraZeneca Young Investigator award.


  • PhD in Cancer Research, University of Manchester, 2006
  • MSc in Biotechnology, Jagiellonian University, Krakow, Poland, 2002


Aga Gambus graduated with MSci from Jagiellonian University, Krakow, Poland. She undertook her Master’s project with Prof Wolfhard Bandlow at LMU, Munich, (2000-2002).

Aga joined Dr Karim Labib’s laboratory at Paterson Institute for Cancer Research, Manchester, for a PhD project (2002-2006). She identified and characterized a large protein complex built around the eukaryotic replicative helicase at DNA replication forks, named the Replisome Progression Complex (RPC). This work shed light onto the way in which the eukaryotic replisome is organized at the replication forks. During a short post-doctoral position, she also showed that one of the components of the RPC: Ctf4, is responsible for connecting the helicase complex to DNA polymerase alpha at the lagging strand of replication forks.

Aga was awarded the CR-UK Pontecorvo prize in 2007 for the best PhD thesis from CR-UK-funded students and received the Michael Dexter Young Investigator award in 2006. 

Following her PhD work, Aga was awarded a Sir Henry Wellcome Fellowship to continue the research towards understanding the architecture of replication machinery. She joined Prof Julian Blow’s laboratory at the Wellcome Trust Centre for Gene Regulation and Expression, Dundee (2007-2011). Using Xenopus laevis egg extract system, she showed that inactive core of replicative helicase (Mcm2-7 complex) is loaded onto origins of replication in the form of double hexamers. These results suggest that an Mcm2-7 double hexamer can initiate a bidirectional pair of forks during S phase, explaining one of the fundamental rules of DNA replication.

Aga joined School of Cancer Sciences in 2011 where she started her independent research. In 2012 she was awarded MRC Career Development Award Fellowship to study the roles of ubiquitin and SUMO during chromosomal DNA replication. She was also awarded Birmingham Fellowship by University of Birmingham. Aga’s group found that polyubiquitylation of replicative helicase plays a crucial role in replication machinery disassembly at the termination of eukaryotic DNA replication forks. The termination stage of DNA replication is hugely understudied and the aim of Aga’s research is therefore to fill in this gap and dissect the details of the mechanism of this process.

In 2015 Aga was awarded Lister Institute Research Award and BACR/AstraZeneca Young Investigator award.


  • Tutor on “Genetic basis of cancer” within MBChB module ‘Cancer: Causes to Cures’.
  • BMedSc Year 3 course “DNA damage pathways in human disease”
  •  BSc Biomedical Science Year 1 course: “Cellular Biochemistry and Biology”
  •  Masterclass for MIBTP PhD students
  •  Supervising PhD, masters, ERASMUS, summer and undergraduate students

Postgraduate supervision

Dr Aga Gambus is interested in supervising doctoral research students in the following areas:

  • Regulation of eukaryotic DNA replication
  • DNA replication and tumor development
  • Novel anticancer therapy targets essential for DNA replication

 If you are interested in studying any of these subject areas please contact Aga on the contact details above. For self-funded students please see: https://www.findaphd.com/search/ProjectDetails.aspx?PJID=54004

Also check out: https://www.birmingham.ac.uk/research/activity/mibtp/index.aspx or for any general doctoral research enquiries, please email: dr@contacts.bham.ac.uk or call +44 (0)121 414 5005.


The role of ubiquitin and SUMO in chromosomal DNA replication

Cell division is the basis for the propagation of life. This involves the precise duplication of genetic information, which is called DNA replication. This process must be, and is, precisely regulated. Any mistakes that are not subsequently repaired can change the way the cell behaves and result in conditions such as genetic diseases, cancer and ageing.

The post-translational modification of proteins by members of the ubiquitin family: specifically ubiquitin and SUMO, is essential to maintain genome stability after DNA damage. Less is known about its role in maintaining genome stability during unperturbed cell cycle: the initiation stage of DNA replication depends on ubiquitin-mediated proteolysis but a growing body of evidence suggests that the further stages of DNA replication are also regulated by these modifications. There are indications that ubiquitin/SUMO ligases play an important role during unperturbed DNA replication, but the proteins they modify are mostly unknown.

Importantly, Aga’s group found that polyubiquitylation of replicative helicase (the protein complex that unwinds DNA) plays a crucial role in replication machinery disassembly at the termination of eukaryotic DNA replication forks. The termination stage of DNA replication is hugely understudied and the aim of Aga’s research is therefore to fill in this gap and dissect the details of the mechanism of this process. It is also important to decipher what part the deregulation of replication termination plays in tumorigenesis.

Aga’s lab investigate replication in cell free system of Xenopus laevis egg extract and in human immortalized cell lines. The projects in the lab encompass also other aspects of ubiquitin and SUMO regulation of DNA replication and damage.

Research Groups and Centres:  BCGB 

Other activities

  • Reviewer for grant funding bodies and journals.
  • Member of Panel V Research Area: Signalling in Biochemical Society
  • Member of The Biochemical Society, British Association for Cancer Research (BACR),  European Association for Cancer Research (EACR), British Society for Cell Biology (BSCB), EMBO Expert Women in Life Sciences (WiLS)
  • External PhD examiner


Sonneville R, Moreno SP, Knebel A, Johnson C, Hastie CJ, Gartner A, Gambus A, Labib K.  CUL-2LRR-1 and UBXN-3 drive replisome disassembly during DNA replication termination and mitosis.  Nat Cell Biol. 2017 Apr 3. doi: 10.1038/ncb3500.

Moreno SP, Bailey R, Campion N, Herron S, Gambus A. Polyubiquitylation drives replisome disassembly at the termination of DNA replication. Science. 2014 Oct 24;346(6208):477-81. doi: 10.1126/science.1253585.

This manuscript has been made available as open access by Science:



Full Text: 

  • Priego Moreno S, Gambus A. Regulation of DNA replication through protein ubiquitylation. Genes 2015 Jun 25;6(3):451-68. doi: 10.3390/genes6030451.
  • Bailey R, Priego Moreno S, Gambus A. Termination of DNA replication forks: “Breaking up is hard to do”. An Extra View on ‘Polyubiquitylation drives replisome disassembly at the termination of DNA replication’. Nucleus, 2015 May 4;6(3):187-96. doi: 10.1080/19491034.2015.1035843. Epub 2015 Apr 2.
  • Gambus A, Blow JJ. Mcm8 and Mcm9 form a dimeric complex in Xenopus laevis egg extract that is not essential for DNA replication initiation.Cell Cycle. 2013 Mar 21;12(8).
  • Gillespie PJ*, Gambus A*, Blow JJ (2012)Preparation and use of Xenopus egg extracts to study DNA replication and chromatin associated proteins. Methods, Apr 19. PMID: 22521908
  • ^Gambus A, Khoudoli GA, Jones RC, Blow JJ (2011) Mcm2-7 Form Double Hexamers At Licensed Origins In Xenopus Egg Extract J Biol Chem. Apr 1;286(13):11855-64. Epub 2011 Jan 31. PMID: 21282109
  • ^Gambus A*, van Deursen F*, Polychronopoulos D, Foltman M, Jones RC, Edmondson RD, Calzada A, Labib K (2009) A key role for Ctf4 in coupling the MCM2-7 helicase to DNA polymerase alpha within the eukaryotic replisome. EMBO J. Oct 7;28(19):2992-3004. Epub 2009 Aug 6. PMID: 19661920
  • Gambus A, Jones R, Sanchez-Diaz A, Kanemaki M, van Deursen F, Edmondson R, Labib K. (2006) GINS maintains association of Cdc45 with MCM in replisome progression complexes at eukaryotic DNA replication forks. Nature Cell BiologyApr;8(4):358-66. Epub 2006 Mar 12. PMID: 16531994
  • Kanemaki M, Sanchez-Diaz A, Gambus A, Labib K. (2003) Functional proteomic identification of DNA replication proteins by induced proteolysis in vivo. Nature. Jun 12;423(6941):720-4. Epub 2003 May 25. PMID: 12768207