Research Interest:

Accurate and timely propagation of genetic information across multiple generations of dividing cells is an essential process initiated by DNA replication and completed by segregation of intact and duplicated copies of the genome. The process of DNA replication relies on the precisely coordinated action of numerous proteins with complementary enzymatic activities of the ‘replisome’, a powerful molecular machine responsible for unwinding the parental DNA template and synthesizing nascent DNA. However, a plethora of endogenous and exogenous threats challenge accurate genome duplication, with perturbation of DNA replication dynamics frequent in cancer cells and underlying the cause of accelerated ageing, inflammatory response, and a range of developmental disorders. To counteract such ‘replication stress, defined as the pausing/stalling of individual replication fork progression, cells mount replisome-based genome surveillance that orchestrates replication speed modulations, replication fork stability, cell cycle progression, replication initiation, and DNA repair. 

In our recently established lab, we are interested in exploring the molecular mechanisms that allow mammalian cells to fully and faithfully replicate their DNA content, repair their broken DNA, and align physiological cell cycle states to continuously varying cell metabolic conditions. To this end, we combine classical cell biology, biochemistry, genetics and quantitative mass spectrometry with state-of-the-art light imaging methodologies such as automated high-content microscopy and AI-assisted image analysis at single-cell resolution. Our research is performed employing mammalian cell culture models of early development and cancer, where we induce physiological metabolic stress, chromatin perturbations, and replication stress, together with genetic manipulations (siRNA and CRISPR) to identify previously concealed genome safeguard mechanisms and cellular responses to genotoxic stress.

Current Project Directions:

• Fundamental principles of replication fork velocity, replisome integrity, and S-phase checkpoint

• Molecular links between metabolic fluctuations and active replisome

• Metabolic coupling of core cell cycle machineries and their roles during genome duplication and mitosis

• Role of homology-directed repair (BRCA-RAD51 pathway) and 53BP1-Sheildin complex during hormone-induced cell proliferation and tissue tropism in cancer

• Link between DNA replication stress and innate immune signaling

Selected Publications:

• PAF15-PCNA assembly exhaustion governs lagging strand replication and replisome integrity. Gita Chhetri, Sugith Babu Badugu, Narcis-Adrian Petriman, Mikkel Bo Petersen, Ganesha Pandian Pitchai, Aylin Seren Güller, Jan Novotný, Barath Balarasa, Morten Frendø Ebbesen, Frederik Tibert Larsen, Tina Ravnsborg, Anoop Kumar Yadav, Anita Lunding, Hana Polasek-Sedlackova, Ole Nørregaard Jensen, Kim Ravnskjaer, Jonathan R. Brewer, Jesper Grud Skat Madsen, Jens S. Andersen, and Kumar Somyajit*. (pre-print at bioRxiv; doi: https://doi.org/10.1101/2025.03.15.641049).

  *- corresponding author

• Metabolic control of replisome plasticity in genome surveillance. Petersen MB, Chhetri G, Somyajit K*. Trends Cell Biol. 2025 Feb 12:S0962-8924(25)00028-5. *- corresponding author

• Oncohistone-sculpted Epigenetic Mechanisms in Pediatric Brain Cancer. Pandey DP* and Somyajit K*, Curr Opin Pharmacol. 2025 Apr;81:102505. *- corresponding authors

• Homologous Recombination as a Fundamental Genome Surveillance Mechanism during DNA Replication. Spies J, Sedlackova H, Lukas J*, Somyajit K*.  Genes (Basel). 2021 Dec 9;12(12):1960.  *- Corresponding authors. (Review)

• Homology-directed repair protects the replicating genome from metabolic assaults. Somyajit K#*, Spies J#, Coscia F, Kirik U, Rask MB, Lee JH, Neelsen KJ, Mund A, Jensen LJ., Paull. TT, Mann M, Lukas J*. Dev Cell. 2021 Feb 22;56(4):461-477.  #-  contributed equally  *- Corresponding authors. 

• Redox-sensitive alteration of replisome architecture safeguards genome integrity. Somyajit K, Gupta R, Sedlackova H, Neelsen KJ, Ochs F, Rask MB, Choudhary C, Lukas J. Science. 2017 Nov 10;358(6364):797-802.

• The equilibrium of nascent and parental MCMs safeguards replicating genomes. Sedlackova H, Rask MB, Gupta R, Choudhary C, Somyajit K*, Lukas J*. Nature 20 Nov;587(7833):297-302. *- Corresponding authors

• DNA Repair Network Analysis Reveals Shieldin as a Key Regulator of NHEJ and PARP Inhibitor Sensitivity. Gupta R, Somyajit K, Narita T, Maskey E, Stanlie A, Kremer M, Typas D, Lammers M, Mailand N, Nussenzweig A, Lukas J, Choudhary C. Cell. 2018 May 3;173(4):972-988.e23.

• Mammalian RAD51 paralogs protect nascent DNA at stalled forks and mediate replication restart. Somyajit K, Saxena S, Babu S, Mishra A, Nagaraju G. Nucleic Acids Res. 2015 Nov 16;43(20):9835-55.

• ATR Signaling Uncouples the Role of RAD51 Paralogs in Homologous Recombination and Replication Stress Response. Saxena S, Dixit S, Somyajit K*, Nagaraju G*. Cell Rep. 2019 Oct15;29(3):551-559.e4. *- Corresponding authors. 

• XRCC2 Regulates Replication Fork Progression during dNTP Alterations. Saxena S, Somyajit K*, Nagaraju G*. Cell Rep. 2018 Dec; 18;25(12):3273-3282.e6. *- Corresponding authors.

Full publication list:

PubMed

SDU

Funding Sources:

Join Us

We are always on the lookout for highly talented, motivated, and team-playing colleagues to join us.

If you are a postdoc candidate, have a strong background in cell cycle, genome integrity, and quantitative cell biology, and are interested in doing interdisciplinary research, please go through our recent papers. If you find our recent work exciting and would like to join us, please send Kumar Somyajit your CV and contact details of three references. Unfortunately, not always a fully funded position is available, but we will support your postdoc fellowship application to Danish and European funding agencies. 

Interested Ph.D. students are also welcome to enquire about applying for funding.  We are looking forward to applications of Individual Study Activity (ISA), Bachelor and Master students in our lab.