Cancer Predisposition Pathways

The Morris lab is interested in the way our cells maintain and repair our genome, and how they protect the genetic information contained within our DNA from damage.

One of our focus areas is exploring the ways the breast and ovarian cancer predisposition protein, BRCA1, and BRCA1’s partner proteins, work in controlling accurate DNA repair via a process called resection, and in protecting cells from DNA damage that occurs in replication. In addition, modification of proteins by chemical groups or small proteins, such as ubiquitin and SUMO, change the way that proteins behave in order to aid DNA repair and DNA replication and we are interested in studying these processes. We look at the way the cell normally controls these modification and DNA damage response pathways and we compare them to changes that occur in cancer cells.

• RCA1 pathways in cancer predisposition and treatment
• Regulation of SUMO in DNA double-strand break repair

Isomerization of BRCA1-BARD1 promotes replication fork protection. Daza-Martin M, Starowicz K, Jamshad M, Tye S, Ronson GE, MacKay HL, Chauhan AS, Walker AK, Stone HR, Beesley JFJ, Coles JL, Garvin AJ, Stewart GS, McCorvie TJ, Zhang X, Densham RM, Morris JR. Nature. 2019 Jul;571(7766):521-527. doi: 10.1038/s41586-019-1363-4. Epub 2019 Jul 3. PMID: 31270457

The deSUMOylase SENP2 coordinates homologous recombination and nonhomologous end joining by independent mechanisms. Garvin AJ, Walker AK, Densham RM, Chauhan AS, Stone HR, Mackay HL, Jamshad M, Starowicz K, Daza-Martin M, Ronson GE, Lanz AJ, Beesley JF, Morris JR. Genes Dev. 2019 Mar 1;33(5-6):333-347. doi: 10.1101/gad.321125.118. Epub 2019 Feb 22. PMID: 30796017

USP48 restrains resection by site-specific cleavage of the BRCA1 ubiquitin mark from H2A. Uckelmann M, Densham RM, Baas R, Winterwerp HHK, Fish A, Sixma TK, Morris JR. Nat Commun. 2018 Jan 15;9(1):229. doi: 10.1038/s41467-017-02653-3. PMID: 29335415

Human BRCA1-BARD1 ubiquitin ligase activity counteracts chromatin barriers to DNA resection. Densham RM, Garvin AJ, Stone HR, Strachan J, Baldock RA, Daza-Martin M, Fletcher A, Blair-Reid S, Beesley J, Johal B, Pearl LH, Neely R, Keep NH, Watts FZ, Morris JR. Nat Struct Mol Biol. 2016 Jul;23(7):647-55. doi: 10.1038/nsmb.3236. Epub 2016 May 30. PMID: 27239795

The deSUMOylase SENP7 promotes chromatin relaxation for homologous recombination DNA repair. Garvin AJ, Densham RM, Blair-Reid SA, Pratt KM, Stone RM, Weekes D, Lawrence KJ, and Morris JR. EMBO reports (2013) 14(11) 975-83. doi: 10.1038/embor.2013.141

Postdocs:

• Ruth Densham
• Alex Garvin
• Katarzyna Starowicz
• George Ronson
• Alexandra Walker
• Anoop Singh Chauhan
• Hannah Mackay
• Mohammed Jamshad

Students:

• Alexander Lanz
• Katherine Ellis
• Matt MacKintosh
• Libby Anthony
• James Beesley