Crossan Lab

Most surprisingly, upon loss of TLS there is a genome-wide failure of DNA demethylation: a critical step in the process of epigenetic reprogramming during germ cell development, as well as a failure to engage the germ cell transcriptional network.

In embryonic germ cells loss of the TLS pathway results in increased DNA damage, activation of cell cycle arrest, and the induction of apoptosis - leading to an over 99% reduction in embryonic germ cells and ultimately leading to complete sterility of adults.

Delighted to share our most recent paper explaining why DNA Translesion Synthesis (TLS) is required for fertility. Huge amount of work from @Pranay_Shahh and a great collaboration with @ReikLab at Altos Labs, @HGLeitch and the Garaycoechea Lab @_Hubrecht Institute (link below)

In summary, we find that the Fanconi anemia crosslink repair pathway acts as a ‘fail-safe’ to prevent L1 retrotransposition when other canonical restriction mechanisms are absent. 9/9

Finally, we show that not only embryonic but also maternal factors are important to suppress L1 retrotransposition at the earliest stages of development 8/n

Very excited to share our latest work nature.com/articles/s4159… published in @NatureSMB ! We find that the Fanconi Anemia DNA crosslink repair pathway restricts L1 retrotransposition during mouse development 🐭🧬 🧵 1/n

We’d like to thank the @HGLeitch lab and @ReikLab for a wonderful collaboration facilitating the exciting discoveries of this study! There is more data than we could highlight here so please do give the pre-print a read! 9/9

In all, TLS components are dispensable in the somatic lineages but essential in the germline. PGCs lacking TLS factors fail to express germline genes or perform global DNA demethylation showing a developmental block, explaining infertility of TLS-deficient organisms
 8/9

Excited for the pre-print of our latest work to go public! In this study, we discovered that DNA damage tolerance is required for mammalian primordial germ cell DNA demethylation and development biorxiv.org/content/10.110… Fantastic collaboration with @ReikLab @HGLeitch 1/9