{"id":285357,"date":"2024-09-20T11:29:18","date_gmt":"2024-09-20T09:29:18","guid":{"rendered":"https:\/\/dhcp205002.cbm.uam.es\/?page_id=285357"},"modified":"2026-03-26T14:23:42","modified_gmt":"2026-03-26T13:23:42","slug":"genome-maintenance-and-variability-enzymology-of-dna-replication-and-repair","status":"publish","type":"page","link":"https:\/\/www.cbm.uam.es\/index.php\/scientific-programs\/genome-dynamics-and-function\/genome-integrity\/genome-maintenance-and-variability-enzymology-of-dna-replication-and-repair\/","title":{"rendered":"Genome maintenance and variability: enzymology of DNA replication and repair"},"content":{"rendered":"<p>[et_pb_section fb_built=&#8221;1&#8243; _builder_version=&#8221;4.27.0&#8243; _module_preset=&#8221;default&#8221; background_color=&#8221;#34609B&#8221; background_image=&#8221;https:\/\/www.cbm.uam.es\/wp-content\/uploads\/2024\/07\/iStock-155145178jpeg-scaled.jpg&#8221; background_position=&#8221;bottom_center&#8221; background_vertical_offset=&#8221;32%&#8221; min_height=&#8221;352px&#8221; height=&#8221;294px&#8221; da_disable_devices=&#8221;off|off|off&#8221; global_colors_info=&#8221;{}&#8221; da_is_popup=&#8221;off&#8221; da_exit_intent=&#8221;off&#8221; da_has_close=&#8221;on&#8221; da_alt_close=&#8221;off&#8221; da_dark_close=&#8221;off&#8221; da_not_modal=&#8221;on&#8221; da_is_singular=&#8221;off&#8221; da_with_loader=&#8221;off&#8221; da_has_shadow=&#8221;on&#8221;][et_pb_row column_structure=&#8221;2_5,3_5&#8243; use_custom_gutter=&#8221;on&#8221; gutter_width=&#8221;4&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; background_color=&#8221;RGBA(255,255,255,0)&#8221; custom_margin=&#8221;61px||||false|false&#8221; custom_padding=&#8221;||0px|||&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_column type=&#8221;2_5&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; background_color=&#8221;rgba(52,96,155,0.83)&#8221; custom_padding=&#8221;50px||50px|50px|false|false&#8221; border_radii=&#8221;on|15px|15px|15px|15px&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_text _builder_version=&#8221;4.25.0&#8243; _module_preset=&#8221;default&#8221; text_text_color=&#8221;#FFFFFF&#8221; custom_margin=&#8221;0px||10px||false|false&#8221; custom_padding=&#8221;0px||0px||false|false&#8221; global_colors_info=&#8221;{}&#8221;]<\/p>\n<p>Scientific Program<\/p>\n<p>[\/et_pb_text][et_pb_heading title=&#8221;Genome dynamics and function&#8221; _builder_version=&#8221;4.27.0&#8243; _module_preset=&#8221;default&#8221; title_font=&#8221;Montserrat||||||||&#8221; title_text_color=&#8221;#FFFFFF&#8221; title_font_size=&#8221;43px&#8221; global_colors_info=&#8221;{}&#8221;][\/et_pb_heading][\/et_pb_column][et_pb_column type=&#8221;3_5&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; custom_padding=&#8221;157px||||false|false&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_text _builder_version=&#8221;4.27.5&#8243; _module_preset=&#8221;default&#8221; global_colors_info=&#8221;{}&#8221; theme_builder_area=&#8221;post_content&#8221;]<\/p>\n<h4 style=\"text-align: center;\"><span style=\"color: #13b5bd;\">UNITS IN THIS PROGRAM<br \/>\n<\/span><\/h4>\n<hr \/>\n<h6 style=\"text-align: center;\"><span style=\"color: #abb8c3;\"><br \/>\n<a href=\"\/index.php\/scientific-programs\/genome-dynamics-and-function\/genome-decoding\/\">Genome decoding<\/a><\/span>\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0<span style=\"color: #13b5bd;\"><a href=\"\/index.php\/scientific-programs\/genome-dynamics-and-function\/genome-integrity\/\">Genome Integrity<\/a><\/span><\/h6>\n<p>[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=&#8221;1&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; background_enable_image=&#8221;off&#8221; background_size=&#8221;custom&#8221; background_image_height=&#8221;84%&#8221; background_position=&#8221;bottom_right&#8221; custom_margin=&#8221;||0px||false|false&#8221; custom_padding=&#8221;||0px||false|false&#8221; da_disable_devices=&#8221;off|off|off&#8221; global_colors_info=&#8221;{}&#8221; da_is_popup=&#8221;off&#8221; da_exit_intent=&#8221;off&#8221; da_has_close=&#8221;on&#8221; da_alt_close=&#8221;off&#8221; da_dark_close=&#8221;off&#8221; da_not_modal=&#8221;on&#8221; da_is_singular=&#8221;off&#8221; da_with_loader=&#8221;off&#8221; da_has_shadow=&#8221;on&#8221;][et_pb_row _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; custom_margin=&#8221;||0px||false|false&#8221; custom_padding=&#8221;||0px||false|false&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_column type=&#8221;4_4&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_heading title=&#8221;RESEARCH GROUP&#8221; _builder_version=&#8221;4.25.0&#8243; _module_preset=&#8221;default&#8221; title_level=&#8221;h5&#8243; title_text_color=&#8221;#13B5BD&#8221; custom_margin=&#8221;50px||0px||false|false&#8221; global_colors_info=&#8221;{}&#8221;][\/et_pb_heading][et_pb_blurb title=&#8221;Genome maintenance and variability: enzymology of DNA replication and repair&#8221; use_icon=&#8221;on&#8221; font_icon=&#8221;&#xe046;||divi||400&#8243; icon_color=&#8221;#13B5BD&#8221; icon_placement=&#8221;left&#8221; image_icon_width=&#8221;26px&#8221; content_max_width=&#8221;1100px&#8221; content_max_width_tablet=&#8221;1100px&#8221; content_max_width_last_edited=&#8221;off|desktop&#8221; _builder_version=&#8221;4.27.0&#8243; header_level=&#8221;h1&#8243; header_font=&#8221;Montserrat||||||||&#8221; header_text_color=&#8221;#000000&#8243; header_font_size=&#8221;29px&#8221; header_line_height=&#8221;1.4em&#8221; body_font=&#8221;||||||||&#8221; body_font_size=&#8221;15px&#8221; body_line_height=&#8221;1.8em&#8221; image_icon_custom_margin=&#8221;6px||||false|false&#8221; background_layout=&#8221;dark&#8221; custom_margin=&#8221;|||&#8221; custom_padding=&#8221;||14px||false|false&#8221; animation_style=&#8221;slide&#8221; animation_direction=&#8221;right&#8221; animation_intensity_slide=&#8221;10%&#8221; animation=&#8221;off&#8221; image_max_width=&#8221;64px&#8221; global_colors_info=&#8221;{}&#8221;][\/et_pb_blurb][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=&#8221;1&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; background_color=&#8221;rgba(175,218,249,0.18)&#8221; custom_padding=&#8221;0px||0px||false|false&#8221; da_disable_devices=&#8221;off|off|off&#8221; global_colors_info=&#8221;{}&#8221; da_is_popup=&#8221;off&#8221; da_exit_intent=&#8221;off&#8221; da_has_close=&#8221;on&#8221; da_alt_close=&#8221;off&#8221; da_dark_close=&#8221;off&#8221; da_not_modal=&#8221;on&#8221; da_is_singular=&#8221;off&#8221; da_with_loader=&#8221;off&#8221; da_has_shadow=&#8221;on&#8221;][et_pb_row column_structure=&#8221;1_4,3_4&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_column type=&#8221;1_4&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_image src=&#8221;\/imgs\/123.jpg&#8221; title_text=&#8221;logoRecurso 7&#8243; align=&#8221;right&#8221; module_class=&#8221;roundedImg&#8221; _builder_version=&#8221;4.27.0&#8243; _module_preset=&#8221;default&#8221; global_colors_info=&#8221;{}&#8221;][\/et_pb_image][\/et_pb_column][et_pb_column type=&#8221;3_4&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_heading title=&#8221;Luis Blanco&#8221; _builder_version=&#8221;4.27.0&#8243; _module_preset=&#8221;default&#8221; title_level=&#8221;h3&#8243; title_text_align=&#8221;left&#8221; title_text_color=&#8221;#008C93&#8243; global_colors_info=&#8221;{}&#8221;][\/et_pb_heading][et_pb_text _builder_version=&#8221;4.27.3&#8243; _module_preset=&#8221;default&#8221; custom_margin=&#8221;-27px||||false|false&#8221; link_option_url_new_window=&#8221;on&#8221; global_colors_info=&#8221;{}&#8221;]<\/p>\n<p style=\"text-align: left;\"><a href=\"https:\/\/x.com\/lblancodavila1?lang=es\" target=\"_blank\" rel=\"noopener\"><img decoding=\"async\" class=\"wp-image-277817 alignleft size-full\" style=\"margin-top: -2px; margin-left: -2px;\" src=\"\/wp-content\/uploads\/2024\/01\/ico_twitter.png\" alt=\"\" width=\"24\" height=\"25\" \/><\/a><br \/><a href=\"https:\/\/orcid.org\/0000-0001-5558-4435\" target=\"_blank\" rel=\"noopener\">ORCID<\/a><\/p>\n<p>[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=&#8221;1&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; background_color=&#8221;#13B5BD&#8221; custom_margin=&#8221;0px||0px||false|false&#8221; custom_padding=&#8221;0px||0px||false|false&#8221; da_disable_devices=&#8221;off|off|off&#8221; global_colors_info=&#8221;{}&#8221; da_is_popup=&#8221;off&#8221; da_exit_intent=&#8221;off&#8221; da_has_close=&#8221;on&#8221; da_alt_close=&#8221;off&#8221; da_dark_close=&#8221;off&#8221; da_not_modal=&#8221;on&#8221; da_is_singular=&#8221;off&#8221; da_with_loader=&#8221;off&#8221; da_has_shadow=&#8221;on&#8221;][et_pb_row column_structure=&#8221;1_3,1_3,1_3&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_column type=&#8221;1_3&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_button button_url=&#8221;#investiga&#8221; button_text=&#8221;Research&#8221; button_alignment=&#8221;center&#8221; _builder_version=&#8221;4.25.0&#8243; _module_preset=&#8221;default&#8221; custom_button=&#8221;on&#8221; button_bg_color=&#8221;#34609B&#8221; animation_style=&#8221;zoom&#8221; global_colors_info=&#8221;{}&#8221;][\/et_pb_button][\/et_pb_column][et_pb_column type=&#8221;1_3&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_button button_url=&#8221;#personal&#8221; 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_module_preset=&#8221;default&#8221; background_enable_image=&#8221;off&#8221; background_size=&#8221;custom&#8221; background_image_height=&#8221;84%&#8221; background_position=&#8221;bottom_right&#8221; custom_margin=&#8221;0px||0px||false|false&#8221; custom_padding=&#8221;0px||15px||false|false&#8221; da_disable_devices=&#8221;off|off|off&#8221; global_colors_info=&#8221;{}&#8221; da_is_popup=&#8221;off&#8221; da_exit_intent=&#8221;off&#8221; da_has_close=&#8221;on&#8221; da_alt_close=&#8221;off&#8221; da_dark_close=&#8221;off&#8221; da_not_modal=&#8221;on&#8221; da_is_singular=&#8221;off&#8221; da_with_loader=&#8221;off&#8221; da_has_shadow=&#8221;on&#8221;][et_pb_row column_structure=&#8221;1_2,1_2&#8243; use_custom_gutter=&#8221;on&#8221; gutter_width=&#8221;2&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; custom_margin=&#8221;20px||||false|false&#8221; custom_padding=&#8221;||||false|false&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_column type=&#8221;1_2&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; global_colors_info=&#8221;{}&#8221;][\/et_pb_column][et_pb_column type=&#8221;1_2&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; custom_padding=&#8221;||||false|false&#8221; global_colors_info=&#8221;{}&#8221;][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=&#8221;3_5,2_5&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; custom_margin=&#8221;||||false|false&#8221; custom_padding=&#8221;0px||||false|false&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_column type=&#8221;3_5&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_heading title=&#8221;Research&#8221; module_id=&#8221;investiga&#8221; _builder_version=&#8221;4.25.0&#8243; _module_preset=&#8221;default&#8221; custom_margin=&#8221;0px|||0px|false|false&#8221; custom_padding=&#8221;3px|||8px|false|false&#8221; border_width_left=&#8221;6px&#8221; border_color_left=&#8221;#34609B&#8221; global_colors_info=&#8221;{}&#8221;][\/et_pb_heading][et_pb_text _builder_version=&#8221;4.27.0&#8243; _module_preset=&#8221;default&#8221; global_colors_info=&#8221;{}&#8221;]<\/p>\n<p style=\"text-align: justify;\">Work done in the last decade has revealed that DNA replication is a major source of genomic instability, due to rearrangements that occur at sites of stalled replication forks. These problems are overall defined as \u201creplication stress\u201d (RS). Along the last five years we have contributed to demostrate that the majority of DNA lesions or blocking structures occurring in the template DNA may be \u201ctolerated\u201d during RS, mainly through the generation of PrimPol-mediated new replicative starting points (namely primers) in the leading strand, immediately beyond the lesion. Importantly, our discovery of PrimPol leads to reconsider the molecular scenario in which the DNA lesion is subsequently repaired, implying the existence of remaining small DNA gaps containing the lesion, generated after PrimPol-mediated restart, that need to be filled, processed, and finally sealed. We are currently interested in the identification and characterization of potential PrimPol interactors, and in the basic mechanism of the subsequent damage tolerance and repair transactions needed behind, after PrimPol-mediated fork restart.<\/p>\n<p>[\/et_pb_text][\/et_pb_column][et_pb_column type=&#8221;2_5&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_image src=&#8221;https:\/\/www.cbm.uam.es\/wp-content\/uploads\/2024\/12\/2024-06-05-Grupo-Luis-Blanco-10Selec-BRILLOS.jpg&#8221; title_text=&#8221;2024-06-05 Grupo Luis Blanco 10Selec BRILLOS&#8221; _builder_version=&#8221;4.27.3&#8243; _module_preset=&#8221;default&#8221; custom_margin=&#8221;60px||||false|false&#8221; custom_padding=&#8221;|||27px||&#8221; animation_style=&#8221;zoom&#8221; border_width_all=&#8221;3px&#8221; border_color_all=&#8221;#13B5BD&#8221; box_shadow_style=&#8221;preset3&#8243; global_colors_info=&#8221;{}&#8221;][\/et_pb_image][\/et_pb_column][\/et_pb_row][et_pb_row _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; custom_padding=&#8221;0px||||false|false&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_column type=&#8221;4_4&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_text _builder_version=&#8221;4.27.0&#8243; _module_preset=&#8221;default&#8221; global_colors_info=&#8221;{}&#8221;]<\/p>\n<p style=\"text-align: justify;\">It is worth mentioning that PrimPol inactivation or removal during the replication of nuclear DNA entails a significant reduction of replication fork speed, indicating its relevant role in physiological conditions. Thus, whereas PrimPol-deficient mice and siRNA-depleted human cells were viable, they show large symptoms of genomic instability, very likely related to the augmented DNA RS in these cells.<\/p>\n<p style=\"text-align: justify;\">On the other hand, in the presence of RS induced by replication inhibitors or topoisomerase poisons, such as camptothecin and etoposide, PrimPol deficiency generates a strong and persistent increase in RS signaling, leading to augmented genetic instability, a hallmark of cancer cells. Altogether, our data strongly suggest that PrimPol is a novel and relevant target in cancer. Its deficiency, either due to specific inactivating mutations or to the use of specific inhibitors, in combination with other well known genotoxic agents, would lead to high replicative stress burden causing tumor cells death by replication catastrophe. Thus, another objective of our research is the analysis of human PrimPol regulation, and the characterization of human PrimPol cancer variants with altered specific activity and primase deficiency, that could have a pronostic value in cancer.<\/p>\n<p style=\"text-align: justify;\">From a biotechnological perspective, we have developed a high-trhougput secreening to obtain PrimPol variants with altered specificity that could be relevant for a novel PrimPol-based DNA amplification method named TruePrime\u2122, currently commercialized by Expedeon AG (currently 4BaseBio AG), for the diagnosis of cancer in liquid biopsies.<\/p>\n<p>[\/et_pb_text][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=&#8221;1&#8243; _builder_version=&#8221;4.23.4&#8243; _module_preset=&#8221;default&#8221; background_color=&#8221;rgba(0,0,0,0.04)&#8221; da_disable_devices=&#8221;off|off|off&#8221; global_colors_info=&#8221;{}&#8221; da_is_popup=&#8221;off&#8221; 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