PhD recipients acquire discipline-specific knowledge and a range of relevant skills during their training in the life sciences, physical sciences, computational sciences, social sciences, and engineering. Empirically testing the applicability of these skills to various careers held by graduates will help assess the value of current training models. This report details results of an Internet survey of science PhDs (n = 8099) who provided ratings for fifteen transferrable skills. Indeed, analyses indicated that doctoral training develops these transferrable skills, crucial to success in a wide range of careers including research-intensive (RI) and non-research-intensive (NRI) careers. Notably, the vast majority of skills were transferrable across both RI and NRI careers, with the exception of three skills that favored RI careers (creativity/innovative thinking, career planning and awareness skills, and ability to work with people outside the organization) and three skills that favored NRI careers (time management, ability to learn quickly, ability to manage a project). High overall rankings suggested that graduate training imparted transferrable skills broadly. Nonetheless, we identified gaps between career skills needed and skills developed in PhD training that suggest potential areas for improvement in graduate training. Therefore, we suggest that a two-pronged approach is crucial to maximizing existing career opportunities for PhDs and developing a career-conscious training model: 1) encouraging trainees to recognize their existing individual skill sets, and 2) increasing resources and programmatic interventions at the institutional level to address skill gaps. Lastly, comparison of job satisfaction ratings between PhD-trained employees in both career categories indicated that those in NRI career paths were just as satisfied in their work as their RI counterparts. We conclude that PhD training prepares graduates for a broad range of satisfying careers, potentially more than trainees and program leaders currently appreciate.

The toroidal damage checkpoint complex Rad9 -Rad1-Hus1 (9-1-1) has been characterized as a sensor of DNA damage. Flap endonuclease 1 (FEN1) is a structure-specific nuclease involved both in removing initiator RNA from Okazaki fragments and in DNA repair pathways. FEN1 activity is stimulated by proliferating cell nuclear antigen (PCNA), a toroidal sliding clamp that acts as a platform for DNA replication and repair complexes. We show that 9-1-1 also binds and stimulates FEN1. Stimulation is observed on a variety of flap, nick, and gapped substrates simulating repair intermediates. Blocking 9-1-1 entry to the double strands prevents a portion of the stimulation. Like PCNA stimulation, 9-1-1 stimulation cannot circumvent the tracking mechanism by which FEN1 enters the substrate; however, 9-1-1 does not substitute for PCNA in the stimulation of DNA polymerase ␦. This suggests that 9-1-1 is a damage-specific activator of FEN1.DNA damage response ͉ DNA replication F lap endonuclease 1 (FEN1) is the primary nuclease involved in the removal of the RNA primers from Okazaki fragments (1). Deletion of the FEN1 gene in Saccharomyces cerevisiae produces temperature-sensitive growth and a phenotype common to DNA replication mutations (2-4). FEN1 is also a key nuclease in long-patch base-excision repair, a major pathway in S. cerevisiae (5-7). FEN1 cleaves a 5Ј flap substrate produced by strand-displacement synthesis during replication or repair. FEN1 cleavage activity is stimulated by proliferating cell nuclear antigen (PCNA) (8-10). In eukaryotes, long-patch base-excision repair was found to be PCNA-dependent (11-13). PCNA encircles the double-stranded region of the flap substrate and improves FEN1 binding to the cleavage site at the base of the flap (10).FEN1 has also been implicated in replication fork restart. A stalled fork can regress into a four-way junction called a chicken foot, which is structurally equivalent to a Holliday recombination junction (14,15). The regression provides a mechanism of damage repair. Werner's protein unwinds this intermediate and creates a substrate for FEN1 (16). The Werner's protein-FEN1 interaction stimulates FEN1 to cleave the strands necessary to restore replication fork structure.DNA damage evokes a cellular response that inhibits DNA replication but allows DNA repair (17). The damage response in eukaryotic cells involves activation of the ATM and ATR proteins. The ATM and ATR kinases activate checkpoint control proteins. ATM is activated in response to double-strand breaks, whereas ATR is activated in response to stalled replication forks and to a variety of damage that causes distortions and single strands (18). Rad9-Rad1-Hus1 (9-1-1) is a toroidal molecule that is loaded onto DNA by Rad17-RFC, a variation of the traditional clamp loader RFC (19). The 9-1-1 complex and ATR are recruited independently to damaged sites (20). The current model suggests that the 9-1-1 complex and ATR act as damage sensors and, therefore, participate in the activation of proteins that promote cell surviva...

The relative importance of reasons for current career choices for science, technology, engineering, and mathematics PhDs was examined. Reasons why underrepresented minority scientists chose faculty careers differed in some respects from those of well-represented scientists, with implications for graduate/postdoctoral training, formal and informal social support networks, and faculty career decisions.

Base excision repair, a major repair pathway in mammalian cells, is responsible for correcting DNA base damage and maintaining genomic integrity. Recent reports show that the Rad9-Rad1-Hus1 complex (9-1-1) stimulates enzymes proposed to perform a long patch-base excision repair sub-pathway (LP-BER), including DNA glycosylases, apurinic/apyrimidinic endonuclease 1 (APE1), DNA polymerase ␤ (pol ␤), flap endonuclease 1 (FEN1), and DNA ligase I (LigI). However, 9-1-1 was found to produce minimal stimulation of FEN1 and LigI in the context of a complete reconstitution of LP-BER. We show here that pol ␤ is a robust stimulator of FEN1 and a moderate stimulator of LigI. Apparently, there is a maximum possible stimulation of these two proteins such that after responding to pol ␤ or another protein in the repair complex, only a small additional response to 9-1-1 is allowed. The 9-1-1 sliding clamp structure must serve primarily to coordinate enzyme actions rather than enhancing rate. Significantly, stimulation by the polymerase involves interaction of primer terminus-bound pol ␤ with FEN1 and LigI. This observation provides compelling evidence that the proposed LP-BER pathway is actually employed in cells. Moreover, this pathway has been proposed to function by sequential enzyme actions in a "hit and run" mechanism. Our results imply that this mechanism is still carried out, but in the context of a multienzyme complex that remains structurally intact during the repair process.The mammalian genome experiences constant stress from both external and internal factors that causes genomic instability. Eukaryotic cells have developed a number of DNA repair pathways that correct DNA damage before it results in permanent chromosomal alteration. Base excision repair (BER) 3 is the major pathway responsible for reversing DNA damage sustained by individual nucleotide bases. Mammalian BER is initiated by DNA glycosylases, which recognize structural alteration of a nitrogenous base and excise it leaving an intact sugarphosphate backbone with an apurinic/apyrimidinic (AP) site (1). AP sites in humans are detected by AP endonuclease 1 (APE1) that cleaves the phosphate backbone of the damaged strand, leaving a nick with a 3Ј-OH group and a 5Ј-deoxyribose phosphate (dRP) residue. The dRP-bordered nick is not a substrate for ligation. If the dRP residue is not oxidized or reduced, repair can proceed via a short patch-BER pathway, in which the dRP residue is removed by the 5Ј-lyase activity of DNA polymerase ␤ (pol ␤), which concurrently fills in the 1-nt gap, and the resulting nick is sealed by the DNA ligase III-XRCC1 complex (2-4).However, if the oxidative state of the dRP is altered, the lyase activity of pol ␤ is inhibited, but the polymerase activity of pol ␤ can still displace the oxidized or reduced dRP residue into a 2-10-nt 5Ј flap intermediate, which will then be cleaved by FEN1 and subsequently joined by LigI (4 -7). This process is known as long patch-base excision repair (LP-BER). Recent studies examining the relevance of the t...