Functional role for the c-Abl tyrosine kinase in meiosis I.
The c-Abl tyrosine kinase is activated by ionizing radiation and certain other DNA-damaging agents. The DNA-dependent protein kinase (DNA-PK) and the ataxia telangiectasia mutated (ATM) gene product, effectors in the DNA damage response, contribute to the induction of c-Abl activity. The present study demonstrates that c-Abl is expressed in mouse and rat testes, and predominantly in pachytene spermatocytes of meiosis I. The results also demonstrate that c-Abl interacts directly with meiotic chromosomes. In concert with a requirement for c-Abl at the pachytene stage, we show that, in contrast to wild-type mice, testes from Abl-/- mice exhibit defects in spermatogenesis. These findings provide the first demonstration that c-Abl plays a functional role in meiosis.
Kharbanda
S
S
Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Pandey
P
P
Morris
P L
PL
Whang
Y
Y
Xu
Y
Y
Sawant
S
S
Zhu
L J
LJ
Kumar
N
N
Yuan
Z M
ZM
Weichselbaum
R
R
Sawyers
C L
CL
Pandita
T K
TK
Kufe
D
D
D000818:Animals; D002875:Chromosomes / Q000502:physiology; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D008540:Meiosis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011494:Protein Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016315:Proto-Oncogene Proteins c-abl / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013090:Spermatocytes / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology; D013194:Staining and Labeling
D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl