Strand invasion by HLTF as a mechanism for template switch in fork rescue

Investor logo
Investor logo
Investor logo

Warning

This publication doesn't include Faculty of Education. It includes Faculty of Medicine. Official publication website can be found on muni.cz.
Authors

BURKOVICS Peter ŠEBESTA Marek BALOGH David HARACSKA Lajos KREJČÍ Lumír

Year of publication 2014
Type Article in Periodical
Magazine / Source Nucleic Acids Research
MU Faculty or unit

Faculty of Medicine

Citation
Doi http://dx.doi.org/10.1093/nar/gkt1040
Field Genetics and molecular biology
Keywords TRANSLESION DNA-SYNTHESIS; CELL NUCLEAR ANTIGEN; HOMOLOGOUS RECOMBINATION; POSTREPLICATION REPAIR; SACCHAROMYCES-CEREVISIAE; REPLICATION FORK; DAMAGED DNA; UBIQUITIN LIGASE; POLYMERASE IOTA; RAD51 PROTEIN
Description Stalling of replication forks at unrepaired DNA lesions can result in discontinuities opposite the damage in the newly synthesized DNA strand. Translesion synthesis or facilitating the copy from the newly synthesized strand of the sister duplex by template switching can overcome such discontinuities. During template switch, a new primer–template junction has to be formed and two mechanisms, including replication fork reversal and D-loop formation have been suggested. Genetic evidence indicates a major role for yeast Rad5 in template switch and that both Rad5 and its human orthologue, Helicase-like transcription factor (HLTF), a potential tumour suppressor can facilitate replication fork reversal. This study demonstrates the ability of HLTF and Rad5 to form a D-loop without requiring ATP binding and/or hydrolysis. We also show that this strand-pairing activity is independent of RAD51 in vitro and is not mechanistically related to that of another member of the SWI/SNF family, RAD54. In addition, the 30-end of the invading strand in the D-loop can serve as a primer and is extended by DNA polymerase. Our data indicate that HLTF is involved in a RAD51-independent Dloop branch of template switch pathway that can promote repair of gaps formed during replication of damaged DNA.
Related projects:

You are running an old browser version. We recommend updating your browser to its latest version.