Josef Jiricny

..This article reviews the progress in our understanding of the mechanism of replication error repair made during the past decade...

..High-resolution crystal structures of DNA complexes with the bacterial MutM protein show how the enzyme feels its way around the double helix in search of an oxidized guanine before flipping it out into its active site and excising it...

..Rai et al. (2008) now report that cytosine demethylation can be accomplished in a one-cell zebrafish embryo by the combined action of a cytidine deaminase and a thymine DNA glycosylase...

..Our analysis also showed novel possible gene targets of microsatellite instability. CONCLUSIONS: MMR inactivation produces distinct changes in the cellular messenger RNA pool, which is consistent with a unique tumorigenesis pathway...

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..Moreover, once DNA methylation damage has been processed by the MMR system, tumor cells might be committed to die, although one or more of their signaling pathways are impaired...

..If hMLH3 participates in MMR in vivo, its partial redundancy with hPMS2, coupled with the fluctuating expression levels of hMLH3, may help explain the low penetrance of hPMS2 mutations in hereditary nonpolyposis colon cancer families...

..The scope of this article is to provide a brief overview of the recent literature on this subject and to raise questions that could be addressed in future studies...

..In vivo this interaction increases during S-phase and may be controlled by the phosphorylation status of the p150 subunit of CAF-1...

..We conclude that molecular dysregulation in slightly elevated, nonpolypoid, precancerous colorectal lesions may be somewhat less severe than that observed in classic adenomatous polyps...

..However, the MMR system still contributes towards cell killing, as MMR deficiency favors the long-term survival of the cells, albeit to a substantially smaller extent than when low MNNG concentrations are deployed...

..Notably, DNA damage signaling proteins played a protective rather than sensitizing role in the MNNG response. Taken together, this evidence demonstrates that (Me)G-containing lesions in yeast must be processed to be cytotoxic...

..During the subsequent S phase, these gaps cause replication fork collapse and elicit recombination and cell cycle arrest...

..The MMR defect in MT1 cells is thus the compound result of one mutation that inactivates the ATPase function of hMutS alpha and a second mutation that apparently destabilizes the Val(1260)Ile hMSH6 protein in human cells in vivo...

..The link of KIAA1018 to the FA pathway is further strengthened by its recruitment to DNA damage through interaction of its UBZ domain with monoubiquitylated FANCD2. We therefore propose to name KIAA1018 FANCD2-associated nuclease, FAN1...

..We conclude that transcription- and replication-dependent pathways contribute to cellular survival following treatment with crosslinking agents...

..These alterations result in significant, inheritable changes in gene expression that contribute to the selection of tumor cells with enhanced survival potential...

..cerevisiae MMR system...

..Our data support the evidence that control of exonuclease 1 activity may be critical for the maintenance of stalled replication forks...

..The protein encoded by PMS2 is also essential for MMR; however, alterations in this gene have been documented only in extremely rare cases. We addressed this unexpected finding by analyzing a large series of CRCs...

..Importantly, ncMMR is not limited to B cells but occurs also in other cell types. Moreover, it contributes to mutagenesis induced by alkylating agents. Activation of ncMMR may therefore play a role in genomic instability and cancer...

..We now report that MMR deficiency reproducibly desensitized cells solely to cisplatin...

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..Surprisingly, although FU is incorporated also into DNA, little is known about its metabolism in this nucleic acid...

..Because polymerase-eta has a propensity to misinsertions opposite adenine residues, the above mechanism would help explain why SHM affects not only C/G, but also A/T base pairs...

..MutLalpha introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXOI to degrade the strand containing the mismatch...

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..This is the first demonstration of a DNA helicase with an intrinsic DNA strand-annealing function residing in a separate domain...

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..This difference may be exploited in gene therapy of tumors with MSI, which represent a substantial proportion of cancers of many different tissues...

..This article reviews our current understanding of this multifaceted DNA-repair system in human cells...

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..The 3D structures of all 12 mispairs formed in the active site of a DNA polymerase help explain their differential effects on polymerase stalling and on translocation of the primer terminus to the enzyme's proofreading site...

..aerophilum ORF PAE2237. We now show that PAE2237 encodes AGOG (Archaeal GO-Glycosylase), the founding member of a new family of DNA glycosylases, which can remove GO from single- and double-stranded substrates with great efficiency...

..We therefore propose that ribonucleotides misincoporated during DNA replication serve as physiological markers of the nascent DNA strand...

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..U mispair in an oligonucleotide substrate to a G.C pair. Interestingly, the efficiency of the in vitro repair reaction was stimulated by Pa-PCNA1, the processivity clamp of DNA polymerases...

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