Telomeres, located at the ends of linear chromosomes, are essential for genome stability and integrity. Advances in telomere researches have linked telomere dysfunction with cellular aging and a number of age-related human diseases. Recent studies further expanded our knowledge of telomere functions - telomeres are shown to be important for microbial pathogen virulence and telomere proteins have important non-telomeric cellular functions.
Thể mút (telomere)
Mỗi thể nhiễm sắc chứa một phân tử ADN liên kết với protein tạo thành các sợi nhiễm sắc xoắn, gấp khúc chạy suốt thể nhiễm sắc. Đầu tận cùng của phân tử ADN ở đầu tận cùng của thể nhiễm sắc được gọi là thể mút. Từ năm 1938, Herman J. Muller gọi đầu tận cùng thể nhiễm sắc là thể mút (telomere) và chứng minh rằng các thể nhiễm sắc bị tác động
tia X làm đứt gãy thể mút sẽ không còn khả năng truyền cho thế hệ sau.
Homologous recombination (HR) serves to eliminate deleterious
lesions, such as double-stranded breaks and interstrand crosslinks,
from chromosomes. HR is also critical for the preservation of replication
forks, for telomere maintenance, and chromosome segregation
in meiosis I. As such, HR is indispensable for the maintenance
of genome integrity and the avoidance of cancers in humans. The
HR reaction is mediated by a conserved class of enzymes termed
Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: A balanced transcription between telomerase and the telomeric DNA-binding proteins TRF1, TRF2 and Pot1 in resting, activated, HTLV-1-transformed and Tax-expressing human T lymphocytes
The 3¢-ends of human chromosomal DNA terminate in short single-stranded guanine-rich tandem-repeat sequences. In cancer cells, these are
associated with the telomere-maintenance enzyme telomerase together with
the end-binding protein hPOT1.
The chromosomal ends ofLeishmania (Leishmania) ama-zonensis contain conserved 5¢-TTAGGG-3¢ telomeric
repeats. Protein complexes that associatein vitro with these
DNA sequences,Leishmania amazonensisG-strand telo-meric protein (LaGT1-3), were identified and characterized
byelectrophoreticmobilityshift assays andUVcross-linking
using protein fractions purified from S100 and nuclear
Telomerase DNA polymerase is unable to replicate the tips of chromosomes, resulting in the loss of DNA at the specialized ends of chromosomes (called telomeres) with each replication cycle. At birth, human telomeres are 15- to 20-kb pairs long and are composed of tandem repeats of a six-nucleotide sequence (TTAGGG) that associate with specialized telomere-binding proteins to form a T-loop structure that protects the ends of chromosomes from being mistakenly recognized as damaged.
Induction of p53 by the DNA damage and oncogene checkpoints.
In response to noxious stimuli, p53 and mdm2 are phosphorylated by the ataxia telangiectasia mutated (ATM) and related ATR serine/threonine kinases, as well as the immediated downstream checkpoint kinases, Chk1 and Chk2. This causes dissociation of p53 from mdm2, leading to increased p53 protein levels and transcription of genes leading to cell cycle arrest (p21Cip1/Waf1) or apoptosis (e.g., the proapoptotic Bcl-2 family members Noxa and Puma).
Replication protein A (RPA) complex has been shown, using bothin vivo
and in vitro approaches, to be required for most aspects of eukaryotic
DNA metabolism: replication, repair, telomere maintenance and homolo-gous recombination.
Telomerase is a specialized reverse transcriptase responsible for synthesizing telomeric DNA at the ends of chromosomes. Six subunits composing the telomerase complex have been cloned: hTR (human telomerase RNA), TEP1 (telomerase-associated protein 1), hTERT (human telomerase reverse transcriptase), hsp90 (heat shock protein 90), p23, and dyskerin. In this study, we investigated the role of each the telomerase subunit on the activity of telomerase.
TheSaccharomyces cerevisiaeatypical protein kinase Bud32p is a member
of the nuclear endopeptidase-like, kinase, chromatin-associated⁄kinase,
endopeptidase-like and other protein of small size (EKC⁄KEOPS) complex,
known to be involved in the control of transcription and telomere homeo-stasis.
One of the most drastic post-translational modification of proteins in eu-karyotic cells is poly(ADP-ribosyl)ation, catalysed by a family enzymes
termed poly(ADP-ribose) polymerases (PARPs). In the human genome, 18
different genes have been identified that all encode PARP family members.