FANCJ helicase controls the balance between shortand long-tract gene conversions between sister chromatids
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FANCJ helicase controls the balance between shortand long-tract gene conversions between sister chromatids. / Nath, Sarmi; Somyajit, Kumar; Mishra, Anup; Scully, Ralph; Nagaraju, Ganesh.
In: Nucleic Acids Research, Vol. 45, No. 15, 2017, p. 8886-8900.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - FANCJ helicase controls the balance between shortand long-tract gene conversions between sister chromatids
AU - Nath, Sarmi
AU - Somyajit, Kumar
AU - Mishra, Anup
AU - Scully, Ralph
AU - Nagaraju, Ganesh
PY - 2017
Y1 - 2017
N2 - The FANCJ DNA helicase is linked to hereditary breast and ovarian cancers as well as bone marrow failure disorder Fanconi anemia (FA). Although FANCJ has been implicated in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR), the molecular mechanism underlying the tumor suppressor functions of FANCJ remains obscure. Here, we demonstrate that FANCJ deficient human and hamster cells exhibit reduction in the overall gene conversions in response to a site-specific chromosomal DSB induced by ISceI endonuclease. Strikingly, the gene conversion events were biased in favour of long-tract gene conversions in FANCJ depleted cells. The fine regulation of short- (STGC) and long-tract gene conversions (LTGC) by FANCJ was dependent on its interaction with BRCA1 tumor suppressor. Notably, helicase activity of FANCJ was essential for controlling the overall HR and in terminating the extended repair synthesis during sister chromatid recombination (SCR). Moreover, cells expressing FANCJ pathological mutants exhibited defective SCR with an increased frequency of LTGC. These data unravel the novel function of FANCJ helicase in regulating SCR and SCR associated gene amplification/duplications and imply that these functions of FANCJ are crucial for the genome maintenance and tumor suppression.
AB - The FANCJ DNA helicase is linked to hereditary breast and ovarian cancers as well as bone marrow failure disorder Fanconi anemia (FA). Although FANCJ has been implicated in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR), the molecular mechanism underlying the tumor suppressor functions of FANCJ remains obscure. Here, we demonstrate that FANCJ deficient human and hamster cells exhibit reduction in the overall gene conversions in response to a site-specific chromosomal DSB induced by ISceI endonuclease. Strikingly, the gene conversion events were biased in favour of long-tract gene conversions in FANCJ depleted cells. The fine regulation of short- (STGC) and long-tract gene conversions (LTGC) by FANCJ was dependent on its interaction with BRCA1 tumor suppressor. Notably, helicase activity of FANCJ was essential for controlling the overall HR and in terminating the extended repair synthesis during sister chromatid recombination (SCR). Moreover, cells expressing FANCJ pathological mutants exhibited defective SCR with an increased frequency of LTGC. These data unravel the novel function of FANCJ helicase in regulating SCR and SCR associated gene amplification/duplications and imply that these functions of FANCJ are crucial for the genome maintenance and tumor suppression.
U2 - 10.1093/nar/gkx586
DO - 10.1093/nar/gkx586
M3 - Journal article
C2 - 28911102
AN - SCOPUS:85031013755
VL - 45
SP - 8886
EP - 8900
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 15
ER -
ID: 197802736