RT Journal Article
T1 C. elegans THSC/TREX-2 deficiency causes replication stress and genome instability
A1 Zheleva, Angelina
A1 Camino, Lola P.
A1 Fernandez-Fernandez, Nuria
A1 Garcia-Rubio, Maria
A1 Askjaer, Peter
A1 Garcia-Muse, Tatiana
A1 Aguilera, Andres
K1 C. elegans
K1 THSC/TREX-2 complex
K1 replication
K1 DNA-RNA hybrids
K1 genome instability
K1 Messenger-rna export
K1 R-loops
K1 Meiotic recombination
K1 Trex-2 complex
K1 Transcription
K1 Protein
K1 Brca2
K1 Yeast
K1 Tho
K1 Impairment
AB Transcription is an essential process of DNA metabolism, yet it makes DNA more susceptible to DNA damage. THSC/TREX-2 is a conserved eukaryotic protein complex with a key role in mRNP biogenesis and maturation that prevents genome instability. One source of such instability is linked to transcription as shown in yeast and human cells, but the underlying mechanism and whether is universal is still unclear. To get further insight in the putative role of THSC/TREX-2 in genome integrity we have used Caenorhabditis elegans mutants of the THP- 1 and DSS-1 members of THSC/TREX-2. These mutants show similar defective meiosis, DNA damage accumulation and activation of the DNA damage checkpoint. However, they differ regarding replication defects as determined by dUTP incorporation in the germline. Interestingly, this specific thp-1 phenotype can be partially rescued by overexpression of RNase H. Furthermore, both mutants show a mild increase in the H3S10P mark previously shown to be linked to DNA-RNA hybrid-mediated genome instability. These data support the view that both THSC/TREX-2 factors prevent transcription-associated DNA damage derived from DNA-RNA hybrid accumulation by separate
PB Company biologists ltd
SN 0021-9533
YR 2021
FD 2021-10-01
LK https://hdl.handle.net/10668/28365
UL https://hdl.handle.net/10668/28365
LA en
DS RISalud
RD Apr 7, 2025