Bloom syndrome helicase contributes to germ line development and longevity in zebrafish

RecQ helicases—also known as the “guardians of the genome”—play crucial roles in genome integrity maintenance through their involvement in various DNA metabolic pathways. Aside from being conserved from bacteria to vertebrates, their importance is also reflected in the fact that in humans impaired function of multiple RecQ helicase orthologs are known to cause severe sets of problems, including Bloom, Werner, or Rothmund-Thomson syndromes. Our aim was to create and characterize a zebrafish (Danio rerio) disease model for Bloom syndrome, a recessive autosomal disorder. In humans, this syndrome is characterized by short stature, skin rashes, reduced fertility, increased risk of carcinogenesis, and shortened life expectancy brought on by genomic instability. We show that zebrafish blm mutants recapitulate major hallmarks of the human disease, such as shortened lifespan and reduced fertility. Moreover, similarly to other factors involved in DNA repair, some functions of zebrafish Blm bear additional importance in germ line development, and consequently in sex differentiation. Unlike fanc genes and rad51, however, blm appears to affect its function independent of tp53. Therefore, our model will be a valuable tool for further understanding the developmental and molecular attributes of this rare disease, along with providing novel insights into the role of genome maintenance proteins in somatic DNA repair and fertility

RecQ helikázokhoz kapcsolható humán betegségek állati modelljei

A szakdolgozatom során a RecQ helikázokhoz kapcsolható betegségeket mutattam be. A RecQ helikázok egy rendkívül fontos fehérjecsalád, aminek az elsődleges feladata a genom szerkezetének a megfelelő fenntartása. Az emberi genomban öt helikáz sorolható ebbe a családba a RECQL1, a BLM, a WRN, a RECQL4 és a RECQL5. A szakdolgozatom során három betegséget és azoknak modellezését mutattam be. A három betegség a Bloom-szindróma, a Werner-szindróma, illetve a Rothmund-Thomson-szindróma volt