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Sixma, Titia

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Titia Sixma studied biochemistry at Utrecht University, The Netherlands. She obtained her PhD (1992) from Groningen University in the group of Wim Hol, studying the crystal structure of Escherichia coli heat-labile enterotoxin (LT), a close relative of cholera toxin. This bacterial protein toxin resembles cholera toxin and its structure determination opened possibilities for drug design against cholera and traveller’s disease.

After a short postdoctoral period in the group of Paul Sigler (Yale University) she returned as group leader to the Netherlands Cancer Institute (since 1994). In 2001 she obtained tenure at the NKI and in 2004 she became part-time bijzonder professor at Erasmus MC.

The Sixma group studies ubiquitin conjugation and DNA repair using a combination of structural methods and biochemistry in order to understand basic cellular processes.

Sixma group website


Key publications

Uckelmann M, Densham RM, Baas R, Winterwerp HHK, Fish A, Sixma TK, Morris JR. (2018)
USP48 restrains resection by site-specific cleavage of the BRCA1 ubiquitin mark from H2A.
Nat Commun. 9:229. doi: 10.1038/s41467-017-02653-3.
Sahtoe DD, van Dijk WJ, Ekkebus R, Ovaa H, Sixma TK. (2016)
BAP1/ASXL1 recruitment and activation for H2A deubiquitination.
Nat Commun. 7:10292. doi: 10.1038/ncomms10292.
Groothuizen FS, Winkler I, Cristóvão M, Fish A, Winterwerp HH, Reumer A, Marx AD, Hermans N, Nicholls RA, Murshudov GN, Lebbink JH, Friedhoff P, Sixma TK.(2015)
MutS/MutL crystal structure reveals that the MutS sliding clamp loads MutL onto DNA.
Elife. 4:e06744. doi: 10.7554/eLife.06744.
Sahtoe DD, van Dijk WJ, El Oualid F, Ekkebus R, Ovaa H, Sixma TK.(2015)
Mechanism of UCH-L5 activation and inhibition by DEUBAD domains in RPN13 and INO80G.
Mol Cell. 57:887-900. doi: 10.1016/j.molcel.2014.12.039.
Mattiroli F, Vissers JH, van Dijk WJ, Ikpa P, Citterio E, Vermeulen W, Marteijn JA, Sixma TK. (2012)
RNF168 ubiquitinates K13-15 on H2A/H2AX to drive DNA damage signaling.
Cell. 150:1182-95 i: 10.1016/j.cell.2012.08.005

Brejc K, van Dijk WJ, Klaassen RV, Schuurmans M, van Der Oost J, Smit AB, Sixma TK (2001)
Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors
Nature 411:269-276 

Lamers MH, Perrakis A, Enzlin JH, Winterwerp HH, de Wind N, Sixma TK (2000)
The crystal structure of DNA mismatch repair protein MutS binding to a G x T mismatch
Nature 407:711-717