Biomedical subjects

S Whitlow

Publications and source records attributed to S Whitlow.

3 recordsLinked to original sources

PubMed2001

Genetic interactions between ATM and the nonhomologous end-joining factors in genomic stability and development.

DNA ligase IV (Lig4) and the DNA-dependent protein kinase (DNA-PK) function in nonhomologous end joining (NHEJ). However, although Lig4 deficiency causes late embryonic lethality, deficiency in DNA-PK subunits (Ku70, Ku80, and DNA-PKcs) does not. Here we demonstrate that, similar to p53 deficiency, ataxia-telangiectasia-mutated (ATM) gene deficiency rescues the embryonic lethality and neuronal apoptosis, but not impaired lymphocyte development, associated with Lig4 deficiency. However, in contrast to p53 deficiency, ATM deficiency enhances deleterious effects of Lig4 deficiency on growth potential of embryonic fibroblasts (MEFs) and genomic instability in both MEFs and cultured progenitor lymphocytes, demonstrating significant differences in the interplay of p53 vs. ATM with respect to NHEJ. Finally, in dramatic contrast to effects on Lig4 deficiency, ATM deficiency causes early embryonic lethality in Ku- or DNA-PKcs-deficient mice, providing evidence for an NHEJ-independent role for the DNA-PK holoenzyme.

Animals↗

PubMed2001

Increased accumulation of hybrid V(D)J joins in cells expressing truncated versus full-length RAGs.

RAG1 and RAG2 (RAGs) initiate V(D)J recombination by introducing breaks between two coding segments and flanking recombination signals (RSs). Nonhomologous end-joining (NHEJ) proteins then join the coding segments and join the RSs. In wild-type cells, both full-length and truncated ("core") RAGs lead to accumulation of "hybrid" V(D)J joins, in which an RS is appended to a different coding sequence. We now show that while hybrid joins do not accumulate in NHEJ-deficient cells that express full-length RAGs, they do accumulate in NHEJ-deficient cells that express the core RAGS; like those catalyzed by core RAGs in vitro, however, they are sealed on just one DNA strand. These results suggest a potential role for the non-core regions in repressing potentially harmful transposition events.

Animals↗

PubMed2000

Amnesia is a deficit in relational memory.

Eye movements were monitored to assess memory for scenes indirectly (implicitly). Two eye movement-based memory phenomena were observed: (a) the repetition effect, a decrease in sampling of previously viewed scenes compared with new scenes, reflecting memory for those scenes, and (b) the relational manipulation effect, an increase in viewing of the regions where manipulations of relations among scene elements had occurred. In normal control subjects, the relational manipulation effect was expressed only in the absence of explicit awareness of the scene manipulations. Thus, memory representations of scenes contain information about relations among elements of the scenes, at least some of which is not accessible to verbal report. But amnesic patients with severe memory impairment failed to show the relational manipulation effect. Their failure to show any demonstrable memory for relations among the constituent elements of scenes suggests that amnesia involves a fundamental deficit in relational (declarative) memory processing.

Adult↗