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Ultimately, MAPK15 inhibition strongly affects telomerase activity, suggesting this kinase as an important player in the mechanisms contributing to bypass replicative senescence and to immortalize cells.
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Taken together, these results suggest that P. aeruginosa: (i) possesses one or more Pols in addition to DinB that contributes to bypass of 4-NQO induced DNA lesions; and (ii) MutS acts to limit errors catalyzed by the Pol(s) used in place of DinB.
Our culture method of hEBs achieved in this study may substantially contribute to bypass or diminish the requirement for the large-scale production of hESCs/hiPSCs and to advance and ensure the quality of hEBs, such as consistent morphological and developmental characteristics (i.e., size, shape, and multi-lineage differentiation potential).
Additionally, our results also show that kinase-switching phenomena can contribute to bypass the loss of EGFR-ligands signalling caused by Ctx because aberrant overactivation of FGFR3 rapidly and efficiently bypasses EGFR-dependency of SCC A431 cells upon loss of AREG/EREG.
In yeast, ATPase mutations do result in growth defects (Budd et al., 2000), and it is possible this is due to the ATPase activity contributing to the bypassing of the RNA primer of Okazaki flaps, as suggested by our in vitro data.
Further analyses are required to identify DNA pols that would be capable of the extension from the various mismatched primer termini opposite γ-OH-PdG, thus, potentially contributing to the mutagenic bypass of this adduct.
Defects in mismatch repair (MMR) are associated with cisplatin resistance by contributing to increased replication bypass of cisplatin adducts and to a drug-tolerant phenotype (Hansen et al, 1998; Karahalil et al, 1998; Hansen and Kelley, 2000; Limp-Foster and Kelley, 2000; O'Neill, 2000).
Alternatively, MutS might recruit DinB to sites of ROS-induced lesions, contributing to their error-prone bypass.
From these results, it was concluded that pol η was not critical to error-free bypass of α-OH-PdG, but it significantly contributed to mutagenic bypass.
The coupling of the EPR effect derived from NP formulations with direct liberation of biologically active SN-38 allowed the treatments to bypass enzymatic activation, contributing to their considerable inhibition of tumor growth in comparison to CPT-11.
Thus, these Pols may contribute to accurate bypass of ROS-induced lesions.
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