Genome Integrity: Facets and Perspectives: 1 (Genome Dynamics and Stability)

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Her lab currently studies various regulatory mechanisms that enable faithful genome duplication and repair. Future work will both deepen the understanding of these processes and explore new regulatory mechanisms in replication and repair.

Sponsors For sponsorship opportunities please contact Perri Wisotsky at pwisotsky nyas. Elegans Sevinc Ercan, PhD, Department of Biology, New York University Condensins are multi-subunit protein complexes that are essential for chromosome condensation during mitosis and meiosis, and play key roles in transcription regulation during interphase.

Metazoans contain two condensins I and II , which perform different functions and localize to different chromosomal regions. The mechanisms by which condensins are targeted to their genomic binding sites remain unclear. Our work indicates that condensin binding is established in two-steps: recruitment and spreading. Recruitment is DNA sequence specific and determined in part by sequence motifs that may be bound by recruiter proteins. Spreading is not sequence specific and occurs onto a subset of active promoters and other intergenic sites.

Here, we will present the results form our ectopic recruitment studies using condensin DC, to understand the factors involved in X—specific recruitment. We will also briefly discuss condensin DC spreading, which increases the level of H4K20me1, a mitosis associated histone modification, and this results in transcription repression.

Facets and Perspectives

We found that loss of ATRX suppresses resolution of sister telomere cohesion at mitosis. Restoration of sister telomere resolution by overexpression of tankyrase 1 or the macroH2A1. Coauthors : Nicole S. Elledge 4,5 , Nikola P. The molecular mechanism that couples this functional change to microtubule attachment status remains unclear.

Dynamics of Genome Reorganization during Human Cardiogenesis

Although the molecular identity of kinetochore components has now been well established, we have just begun to understand the assembly process and spatial arrangement of this dynamic machine. Applying 3-D super-resolution imaging to Xenopus egg extracts, we reveal that the kinetochore is spatially and functionally segmented into a stable core module supporting end-on attachment and an expandable module responsible for lateral attachment and SAC signaling.

Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications

Unexpectedly, the inner kinetochore component CENP-C is an integral component of the expandable module, whose assembly also depends on outer kinetochore proteins Bub1, BubR1 and multiple protein kinases Aurora B, Haspin, Plx1, Mps1 and is suppressed by protein phosphatase 1. We propose that the expandable module consists of a phosphorylation-dependent copolymer that spatially segregates kinetochore functions to help couple end-on attachment and SAC silencing.

This process eliminates nearly all noncoding DNA, including transposons, and rearranges over , short DNA segments to produce tiny gene-sized "nanochromosomes. The whole process produces a mature, somatic genome of over 16, nanochromosomes Swart et al. Hanawalt, P. Transcription-coupled DNA repair: two decades of progress and surprises. Li, X.

Genome Integrity

Cotranscriptional processes and their influence on genome stability. Saxowsky, T. RNA polymerase encounters with DNA damage: transcription-coupled repair or transcriptional mutagenesis? Latella, L. Differentiation-induced radioresistance in muscle cells. Fortini, P. The response to DNA damage during differentiation: Pathways and consequences. Barzilai, A. The contribution of the DNA damage response to neuronal viability. Redox Signal. Du, F. Tightly coupled brain activity and cerebral ATP metabolic rate. Karanjawala, Z. Oxygen metabolism causes chromosome breaks and is associated with the neuronal apoptosis observed in DNA double-strand break repair mutants.

Ju, B. Ming, G.


Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron 70 , — Zhao, C. Mechanisms and functional implications of adult neurogenesis. Spalding, K. Dynamics of hippocampal neurogenesis in adult humans. Shen, J. Date, H. Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene. Moreira, M.

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Trends Biochem. Reynolds, J. Impact of PNKP mutations associated with microcephaly, seizures and developmental delay on enzyme activity and DNA strand break repair. Nucleic Acids Res. Breslin, C.

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The role of double-strand break repair—insights from human genetics. Klingseisen, A. Mechanisms and pathways of growth failure in primordial dwarfism. Thornton, G. Primary microcephaly: do all roads lead to Rome? Griffith, E. Gruber, R. MCPH1 regulates the neuroprogenitor division mode by coupling the centrosomal cycle with mitotic entry through the Chk1-Cdc25 pathway. Higginbotham, H. The centrosome in neuronal development. Wang, X.