With advances in next-generation sequencing technologies, numerous novel transcripts in a large number of organisms have been identified. With the goal of fast, accurate assessment of the coding ability of RNA transcripts, we upgraded the coding potential calculator CPC1 to CPC2. CPC2 runs ∼1000 times faster than CPC1 and exhibits superior accuracy compared with CPC1, especially for long non-coding transcripts. Moreover, the model of CPC2 is species-neutral, making it feasible for ever-growing non-model organism transcriptomes. A mobile-friendly web server, as well as a downloadable standalone package, is freely available at http://cpc2.cbi.pku.edu.cn.

Non-homologous end joining (NHEJ) is a major pathway to repair DNA double-strand breaks (DSBs), which can display different types of broken ends. However, it is unclear how NHEJ factors organize to repair diverse types of DNA breaks. Here, through systematic analysis of the human NHEJ factor interactome, we identify PAXX as a direct interactor of Ku. The crystal structure of PAXX is similar to those of XRCC4 and XLF. Importantly, PAXX-deficient cells are sensitive to DSB-causing agents. Moreover, epistasis analysis demonstrates that PAXX functions together with XLF in response to ionizing radiation-induced complex DSBs, whereas they function redundantly in response to Topo2 inhibitor-induced simple DSBs. Consistently, PAXX and XLF coordinately promote the ligation of complex but not simple DNA ends in vitro. Altogether, our data identify PAXX as a new NHEJ factor and provide insight regarding the organization of NHEJ factors responding to diverse types of DSB ends.

We report the electrochemical growth of gold nanowires with controlled dimensions and crystallinity. By systematically varying the deposition conditions, both polycrystalline and single-crystalline wires with diameters between 20 and 100 nm are successfully synthesized in etched ion-track membranes. The nanowires are characterized using scanning electron microscopy, high resolution transmission electron microscopy, scanning tunnelling microscopy and x-ray diffraction. The influence of the deposition parameters, especially those of the electrolyte, on the nanowire structure is investigated. Gold sulfite electrolytes lead to polycrystalline structure at the temperatures and voltages employed. In contrast, gold cyanide solution favours the growth of single crystals at temperatures between 50 and 65 °C under both direct current and reverse pulse current deposition conditions. The single-crystalline wires possess a [110] preferred orientation.

Long noncoding RNAs (lncRNAs) are emerging as key regulators of multiple essential biological processes involved in physiology and pathology. By analyzing the largest compendium of 14,166 samples from normal and tumor tissues, we significantly expand the landscape of human long noncoding RNA with a high-quality atlas: RefLnc (Reference catalog of LncRNA). Powered by comprehensive annotation across multiple sources, RefLnc helps to pinpoint 275 novel intergenic lncRNAs correlated with sex, age or race as well as 369 novel ones associated with patient survival, clinical stage, tumor metastasis or recurrence. Integrated in a user-friendly online portal, the expanded catalog of human lncRNAs provides a valuable resource for investigating lncRNA function in both human biology and cancer development.

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The replication protein A (RPA) complex binds singlestranded DNA generated at stalled replication forks and recruits other DNA repair proteins to promote recovery of these forks. Here, we identify Ewing tumor-associated antigen 1 (ETAA1), which has been linked to susceptibility to pancreatic cancer, as a new repair protein that is recruited to stalled forks by RPA. We demonstrate that ETAA1 interacts with RPA through two regions, each of which resembles two previously identified RPA-binding domains, RPA70N-binding motif and RPA32C-binding motif, respectively. In response to replication stress, ETAA1 is recruited to stalled forks where it colocalizes with RPA, and this recruitment is diminished when RPA is depleted. Notably, inactivation of the ETAA1 gene increases the collapse level of the stalled replication forks and decreases the recovery efficiency of these forks. Moreover, epistasis analysis shows that ETAA1 stabilizes stalled replication forks in an ataxia telangiectasia and Rad3-related protein (ATR)-independent manner. Thus, our results reveal that ETAA1 is a novel RPA-interacting protein that promotes restart of stalled replication forks.The faithful replication of DNA is essential for the maintenance of genomic stability and the prevention of cancerpromoting mutations. Replication forks can be stalled by numerous obstacles on the DNA template, including unrepaired DNA damage, DNA-bound proteins, and secondary structures (1). Stalled replication forks are able to restart once the obstacles are removed or become broken (collapse) into DNA double strand breaks, which pose the most serious threat to genome integrity when fork protection fails (2, 3). However, how stalled replication forks are protected is not well understood.The replication protein A (RPA) 3 complex, which consists of RPA1 (RPA70), RPA2 (RPA32), and RPA3 (RPA14), plays crucial roles in a variety of DNA metabolic pathways, including DNA replication, recombination, repair, and DNA damage checkpoint (4 -6). When replication forks stalled, singlestranded DNA (ssDNA) is generated and extended by minichromosome maintenance protein complex helicases (7,8). The ssDNA is bound by RPA, which protects ssDNA from cleavage by nucleases and recruits repair proteins to initiate DNA damage responses. The RPA-ssDNA complex recruits and activates ATR/ATRIP thereby eliciting checkpoint signaling (9). In addition, RPA-ssDNA complex also recruits factors necessary for the stabilization and resumption of stalled replication forks, such as RAD51 (10, 11) and SMARCAL1 (12-15). Recently, several studies have also revealed a physical and functional interaction between RPA and the ubiquitin E3 ligases RFWD3 (16 -18) and PRP19 (19), which ubiquitinate RPA and facilitate replication fork restart. Here, we identified a new RPA interaction protein, ETAA1, whose gene variation has been associated with susceptibility to pancreatic cancer (20). ETAA1 is recruited to stalled replication forks in response to replication stress, and the disruption of ETAA1 leads to fork colla...

The MRE11–RAD50–NBS1 (MRN) complex is well known for participating in DNA damage response pathways in all phases of cell cycle. Here, we show that MRN constitutes a mitosis-specific complex, named mMRN, with a protein, MMAP. MMAP directly interacts with MRE11 and is required for optimal stability of the MRN complex during mitosis. MMAP colocalizes with MRN in mitotic spindles, and MMAP-deficient cells display abnormal spindle dynamics and chromosome segregation similar to MRN-deficient cells. Mechanistically, both MMAP and MRE11 are hyperphosphorylated by the mitotic kinase, PLK1; and the phosphorylation is required for assembly of the mMRN complex. The assembled mMRN complex enables PLK1 to interact with and activate the microtubule depolymerase, KIF2A, leading to spindle turnover and chromosome segregation. Our study identifies a mitosis-specific version of the MRN complex that acts in the PLK1–KIF2A signaling cascade to regulate spindle dynamics and chromosome distribution.

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