PMID- 11320209
OWN - NLM
STAT- MEDLINE
DCOM- 20010614
LR  - 20181113
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 98
IP  - 10
DP  - 2001 May 8
TI  - Sequence conservation at human and mouse orthologous common fragile regions, 
      FRA3B/FHIT and Fra14A2/Fhit.
PG  - 5722-7
AB  - It has been suggested that delayed DNA replication underlies fragility at common 
      human fragile sites, but specific sequences responsible for expression of these 
      inducible fragile sites have not been identified. One approach to identify such 
      cis-acting sequences within the large nonexonic regions of fragile sites would be 
      to identify conserved functional elements within orthologous fragile sites by 
      interspecies sequence comparison. This study describes a comparison of 
      orthologous fragile regions, the human FRA3B/FHIT and the murine Fra14A2/Fhit 
      locus. We sequenced over 600 kbp of the mouse Fra14A2, covering the region 
      orthologous to the fragile epicenter of FRA3B, and determined the Fhit deletion 
      break points in a mouse kidney cancer cell line (RENCA). The murine Fra14A2 
      locus, like the human FRA3B, was characterized by a high AT content. Alignment of 
      the two sequences showed that this fragile region was stable in evolution despite 
      its susceptibility to mitotic recombination on inhibition of DNA replication. 
      There were also several unusual highly conserved regions (HCRs). The positions of 
      predicted matrix attachment regions (MARs), possibly related to replication 
      origins, were not conserved. Of known fragile region landmarks, five cancer cell 
      break points, one viral integration site, and one aphidicolin break cluster were 
      located within or near HCRs. Thus, comparison of orthologous fragile regions has 
      identified highly conserved sequences with possible functional roles in 
      maintenance of fragility.
FAU - Shiraishi, T
AU  - Shiraishi T
AD  - Kimmel Cancer Center, Jefferson Medical College, 233 South 10th Street, 
      Philadelphia, PA 19107, USA.
FAU - Druck, T
AU  - Druck T
FAU - Mimori, K
AU  - Mimori K
FAU - Flomenberg, J
AU  - Flomenberg J
FAU - Berk, L
AU  - Berk L
FAU - Alder, H
AU  - Alder H
FAU - Miller, W
AU  - Miller W
FAU - Huebner, K
AU  - Huebner K
FAU - Croce, C M
AU  - Croce CM
LA  - eng
SI  - GENBANK/AF332859
SI  - GENBANK/AF332860
SI  - GENBANK/AF332861
SI  - GENBANK/AF332862
GR  - HG02238/HG/NHGRI NIH HHS/United States
GR  - CA56036/CA/NCI NIH HHS/United States
GR  - T32-CA09678/CA/NCI NIH HHS/United States
GR  - P01 CA077738/CA/NCI NIH HHS/United States
GR  - T32 CA009678/CA/NCI NIH HHS/United States
GR  - P01-CA77738/CA/NCI NIH HHS/United States
GR  - R01 HG002238/HG/NHGRI NIH HHS/United States
GR  - P30 CA056036/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20010424
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proteins)
RN  - 0 (fragile histidine triad protein)
RN  - EC 3.6.- (Acid Anhydride Hydrolases)
SB  - IM
MH  - *Acid Anhydride Hydrolases
MH  - Animals
MH  - Chromosome Fragile Sites
MH  - *Chromosome Fragility
MH  - Exons
MH  - Humans
MH  - Mice
MH  - Molecular Sequence Data
MH  - *Neoplasm Proteins
MH  - Polymerase Chain Reaction
MH  - Proteins/*genetics
MH  - Repetitive Sequences, Nucleic Acid
PMC - PMC33280
EDAT- 2001/04/26 10:00
MHDA- 2001/06/15 10:01
PMCR- 2001/11/08
CRDT- 2001/04/26 10:00
PHST- 2001/04/26 10:00 [pubmed]
PHST- 2001/06/15 10:01 [medline]
PHST- 2001/04/26 10:00 [entrez]
PHST- 2001/11/08 00:00 [pmc-release]
AID - 091095898 [pii]
AID - 0958 [pii]
AID - 10.1073/pnas.091095898 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2001 May 8;98(10):5722-7. doi: 10.1073/pnas.091095898. 
      Epub 2001 Apr 24.