Polη, a Y-family translesion synthesis polymerase, promotes cellular tolerance of Myc-induced replication stress.

Growth of precancerous and cancer cells relies on their tolerance of oncogene-induced replication stress (RS). Translesion synthesis (TLS) plays an essential role in the cellular tolerance of various types of RS and bypasses replication barriers by employing specialized polymerases. However, limited information is available about the role of TLS polymerases in oncogene-induced RS.

Acute HSF1 depletion induces cellular senescence through the MDM2-p53-p21 pathway in human diploid fibroblasts.

Heat shock transcription factor 1 (HSF1) regulates the expression of a wide array of genes, controls the expression of heat shock proteins (HSPs) as well as cell growth. Although acute depletion of HSF1 induces cellular senescence, the underlying mechanisms are poorly understood. Here, we report that HSF1 depletion-induced senescence (HDIS) of human diploid fibroblasts (HDFs) was independent of HSP-mediated proteostasis but dependent on activation of the p53-p21 pathway, partly because of the increased expression of dehydrogenase/reductase 2 (DHRS2), a putative MDM2 inhibitor.

Both high-fidelity replicative and low-fidelity Y-family polymerases are involved in DNA rereplication.

DNA rereplication is a major form of aberrant replication that causes genomic instabilities, such as gene amplification. However, little is known about which DNA polymerases are involved in the process. Here, we report that low-fidelity Y-family polymerases (Y-Pols), Pol η, Pol ι, Pol κ, and REV1, significantly contribute to DNA synthesis during rereplication, while the replicative polymerases, Pol δ and Pol ε, play an important role in rereplication, as expected.

Molecular chaperone Hsp90 regulates REV1-mediated mutagenesis.

REV1 is a Y-family polymerase that plays a central role in mutagenic translesion DNA synthesis (TLS), contributing to tumor initiation and progression. In a current model, a monoubiquitinated form of the replication accessory protein, proliferating cell nuclear antigen (PCNA), serves as a platform to recruit REV1 to damaged sites on the DNA template. Emerging evidence indicates that posttranslational mechanisms regulate REV1 in yeast; however, the regulation of REV1 in higher eukaryotes is poorly understood.

The molecular chaperone Hsp90 regulates accumulation of DNA polymerase eta at replication stalling sites in UV-irradiated cells.

DNA polymerase eta (Pol eta) is a member of the mammalian Y family polymerases and performs error-free translesion synthesis across UV-damaged DNA. For this function, Pol eta accumulates in nuclear foci at replication stalling sites via its interaction with monoubiquitinated PCNA. However, little is known about the posttranslational control mechanisms of Pol eta, which regulate its accumulation in replication foci.

[Fanconi anemia--genotoxic stress and senescence of hematopoietic stem cells].

Fanconi anemia (FA) is a genetically heterogeneous inherited disorder characterized by progressive bone marrow failure, development of hematopoietic and solid malignancies and genomic instability. 13 FA proteins, identified to date, closely cooperate with familial breast cancer susceptibility proteins such as BRCA2 and PALB2, thereby forming 'the FA/BRCA molecular network'. Here I summarize our recent understanding of the molecular network and its significance in the pathogenesis of FA.

Hsp90 and the Fanconi anemia pathway: a molecular link between protein quality control and the DNA damage response.

Heat shock protein 90 (Hsp90) is a molecular chaperone that plays an essential role in cell growth and survival. The chaperone exerts these functions by regulating key signaling proteins involved in cell growth/survival and protecting cells from proteotoxic stress. Importantly, Hsp90 inhibitors including geldanamycin analogues show anti-tumor effects.

Identification, characterization, and developmental regulation of two storage proteins in the bamboo borer Omphisa fuscidentalis.

Two insect storage proteins, OfSP1 (75 kDa) and OfSP2 (72 kDa), were purified using three different chromatographies from the hemolymph of Omphisa fuscidentalis larvae during diapause, and their genes were cloned. OfSP1 and OfSP2 concentrations in the hemolymph were high during diapause. During pupation, OfSP1 levels decreased in the male hemolymph and disappeared from the female hemolymph.