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All cells rely on DNA polymerases to duplicate their genetic material and to repair or bypass DNA lesions. In humans, sixteen polymerases have been identified, and each bears specific functions in genome maintenance. Here, we identified the recently discovered polymerase POLN to be involved in repair of DNA crosslinks. Such DNA lesions are highly toxic, and are believed to be repaired by the sequential activity of nucleotide excision repair, translesionRead more
Left unrepaired, DNA interstrand crosslinks represent impassable hurdles for DNA replication, and their removal is a complicated stepwise process involving a variety of enzymes. In a recent paper in Science, Knipscheer et al. (2009) demonstrate that the Fanconi Anemia protein FANCD2 promotes multiple steps of the crosslink repair process.Read more
Fanconi Anemia (FA) is an inherited genomic instability disorder, caused by mutations in genes regulating replication-dependent removal of interstrand DNA crosslinks. The Fanconi Anemia pathway is thought to coordinate a complex mechanism that enlists elements of three classic DNA repair pathways, namely homologous recombination, nucleotide excision repair, and mutagenic translesion synthesis, in response to genotoxic insults. To this end, the FanconiRead more
The RAD6 pathway is central to post-replicative DNA repair in eukaryotic cells; however, the machinery and its regulation remain poorly understood. Two principal elements of this pathway are the ubiquitin-conjugating enzymes RAD6 and the MMS2-UBC13 heterodimer, which are recruited to chromatin by the RING-finger proteins RAD18 and RAD5, respectively. Here we show that UBC9, a small ubiquitin-related modifier (SUMO)-conjugating enzyme, is also affiliatedRead more
Damaged DNA, if not repaired before replication, can lead to replication fork stalling and genomic instability; however, cells can switch to different damage bypass modes that permit replication across lesions. Two main bypasses are controlled by ubiquitin modification of proliferating cell nuclear antigen (PCNA), a homotrimeric DNA-encircling protein that functions as a polymerase processivity factor and regulator of replication-linked functions.Read more
Accurate segregation of the genetic material during cell division requires that sister chromatids are kept together by cohesion proteins until anaphase, when the chromatids become separated and distributed to the two daughter cells. Studies in yeast revealed that chromatid cohesion is essential for viability and is triggered by the conserved protein Eco1 (Ctf7). Cohesion must be established already in S phase in order to tie up sister chromatidsRead more